Research ArticleSynthesis Characterization and Anticancer Activity ofNew Benzofuran Substituted Chalcones

Demet CoGkun1 Suat Tekin2 Suumlleyman Sandal2 and Mehmet Fatih CoGkun1

1Department of Chemistry Faculty of Science Fırat University 23119 Elazıg Turkey2Department of Physiology Faculty of Medicine Inonu University 44000 Malatya Turkey

Correspondence should be addressed to Demet Coskun dcoskunfiratedutr

Received 6 April 2016 Revised 26 April 2016 Accepted 8 May 2016

Academic Editor Grigoris Zoidis

Copyright copy 2016 Demet Coskun et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diversepharmacological profiles including anticancer activity Similarly chalcones which are common substructures of numerous naturalproducts belonging to the flavonoid class feature strong anticancer properties A novel series of chalcones 3-aryl-1-(5-bromo-1-benzofuran-2-yl)-2-propanones propenones (3andashf) were designed synthesized and characterized In vitro antitumor activitiesof the newly synthesized (3andashf) and previously synthesized (3gndashj) chalcone compounds were determined by using human breast(MCF-7) and prostate (PC-3) cancer cell lines Antitumor properties of all compounds were determined by 3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium bromide (MTT) assay Cell viability assay for the tested chalcone compounds was performed and thelog IC

50values of the compounds were calculated after 24-hour treatment Our results indicate that the tested chalcone compounds

show antitumor activity against MCF-7 and PC-3 cell lines (119901 lt 005)

1 Introduction

Cancer is one of the most important clinical problemsworldwide Among the wide range of compounds approvedas potential anticancer agents derivatives with functionalitiesas 120572120573-unsaturated Michael acceptor have attracted greatinterest [1 2] Previous studies have proposed that anti-cancer compounds such as alkylating agents bind directlyto various cellular nucleophiles thus lacking selectivityHowever Michael acceptors can be structurally modifiedso that they can react selectively with target nucleophiles[3] Chalcones the compounds having 13-diaryl-2-propen-1-one system also have shown a broad spectrum of biologicalactivities including anti-inflammatory [4ndash7] antimalarial [8]anti-invasive [9] antibacterial [10ndash12] and anticancer [13ndash16] activities On the other hand chalcones are capable ofinducing apoptosis [17 18] Consequently these compoundsare recognized as promising anticancer agents [19ndash22] Anumber of clinically useful anticancer drugs have genotoxiceffects because of their interaction with the amino groupsof nucleic acids However chalcones have been found notto show such undesired side effects [23] Numerous reports

have been published on the interesting anti-breast canceractivity shown by chalcones [24ndash26] Benzofuran deriva-tives are an interesting class of heterocyclic compoundsBenzofuran derivatives are of great interest in medicinalchemistry and have drawn remarkable attention due to theirbiological activities with chemotherapeutic properties [27]Some benzofurans bearing various substituents at the C-2 position are greatly distributed in nature for exampleailanthoidol a neolignan derivative has been reported tohave antiviral antioxidant and antifungal activities [28]Furthermore most of the compounds prepared from 2-acetylbenzofuran have antimicrobial anticancer antitumoranti-inflammatory and antitubulin activities and are alsoused for treatment of cardiac arrhythmias [29ndash32] The useof the combinations of different pharmacological compoundsin the design of new drugs may lead to finding novel drugswith interesting biological activity [33 34] Furthermore nostudies were found in the literature evaluating anticancerproperties of benzofuran substituted chalcone derivativesThis encouraged us to synthesize benzofuran substitutedchalcone compounds and to investigate anticancer propertiesof these compounds

Hindawi Publishing CorporationJournal of ChemistryVolume 2016 Article ID 7678486 8 pageshttpdxdoiorg10115520167678486

2 Journal of Chemistry

O

O

O

O

X1

23

4

5 67 8 9 10

1112

1314

15

1617

1

23

4

5 67 8 9 10

11

12

13 14

15R1

R1R2

R3

3a R1 = Br R2 = H R3 = H

3b R1 = Br R2 = H R3 = Br

3c R1 = Br R2 = NO2 R3 = H

3d R1 = Br R2 = H R3 = N(CH3)2

3i R1 = H R2 = H R3 = H

3j R1 = H R2 = H R3 = N(CH3)2

3e R1 = Br X = O

3f R1 = Br X = S

3g R1 = H X = O

3h R1 = H X = S

Scheme 1 Structure of synthetic derivatives 3andash3j

In this study we aimed at designing and synthesizingnew compounds (3andashf) with both benzofuran and chalconeunits in one molecule and examining anticancer activityof this newly synthesized chalcones (3andashf) and previouslysynthesized chalcones [35] (3gndashj) bearing no substituent inthe benzofuran ring as a different series against human breastcancer cell lines (MCF-7) and human prostate cancer cells(PC-3) (Scheme 1)

2 Materials and Methods

21 Materials Chemical agents used in the present studyincluded dimethyl sulfoxide (DMSO Merck Germany)penicillin-streptomycin fetal bovine serum (FBS) andDMEM (Dulbeccorsquos Modified Eagle Medium) Double-distilled water was used at all stages of the experimentsSamples of chalcone compounds for testing were prepared at1 5 25 50 and 100 120583M concentrations

22 Characterization Techniques Melting points were mea-sured using a differential scanning calorimeter (ShimadzuDSC-50) and were uncorrected NMR spectra were deter-mined on a Bruker AC 400 (400MHz) spectrometer withtetramethylsilane (TMS) as the internal standard in DMSO-d6or CDCl

3as solvents FT-Infrared (FT-IR) spectra were

recorded as KBr pellets on a Perkin-Elmer SpectrumOne FT-IR spectrometer

Synthesis of 1-(5-Bromo-1-benzofuran-2-yl)ethanone (D1) Amixture of 4-bromo salicylaldehyde (1 g 497mmol) andpotassium carbonate (069 g 497mmol) in dry acetone(10mL) was stirred at 25∘C for 1 h Reaction mixture wascooled at 0ndash5∘C and then chloroacetone (4mL 497mmol)was added dropwise Reaction mixture was stirred at roomtemperature for ten minutes and then refluxed Progress ofthe reaction was monitored by TLC Upon completion thereaction mixture was poured on crashed iceThe precipitatedsolid was filtered washed with water and dried The product

was crystallized from ethanol (yield 108 gr 91 mp 117ndash119∘C)

FT-IR (KBr cmminus1) 1667 (C=O) 1542 (C=C) 1H-NMR(400MHz DMSO-d

6) ppm 803 (s 1H 5-H) 782 (s 1H 7-

H) 769 (dd 1H 119869 = 86Hz and 119869 = 82Hz 3-H) 765 (d1H 119869 = 88Hz 2-H) 256 (s 3H methyl protons) 13C-NMR(400MHz DMSO-d

6) 18840 15414 15346 13143 12946

12639 11663 11484 11383 2697 Anal Calc C 5024 H295 Found C 5021 H 299

General Procedure for Synthesis of Chalcones (3andashf ) Asolution of 1-(5-bromo-1-benzofuran-2-yl)ethanone (1 g418mmol) and one of the aldehyde derivatives (2andashf418mmol) in MeOH (10mL) was cooled at 0ndash5∘C andthen 6mL of aqueous NaOH (1molL) was added to thissolution and stirred at room temperature for 3 hThe reactionmixture was poured on crushed ice The precipitated solidwas filtered after neutralization with diluted HCl and waswashed several times with water and then driedThe productwas recrystallized from ethanol

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-phenylprop-2-en-1-one(3a) Yield 70 Mp 145ndash147∘C FT-IR (KBr cmminus1) 1655(C=O) 1599 (C=C) 1H-NMR (400MHz DMSO-d

6) ppm

827 (s 1H 5-H) 812 (s 1H 7-H) 792ndash784 (m 4H 13-H17-H 10-H 11-H) 784ndash765 (m 2H 3-H 2-H) 765ndash740 (m3H 16-H 15-H 14-H) 13C-NMR (400MHz DMSO-d

6)

17896 15459 15455 14446 13476 13163 13146 1296412950 12946 12649 12218 11677 11488 11456 Anal Calc C 6241 H 339 Found C 6243 H 343

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(3-bromophenyl)prop-2-en-1-one (3b) Yield 82 Mp 206ndash208∘C FT-IR (KBrcmminus1) 1654 (C=O) 1604 (C=C) 1H-NMR (400MHzDMSO-d

6) ppm 829 (s 1H 5-H) 815 (s 1H 7-H) 800ndash

762 (m 8H 3-H 2-H 17-H 16-H 14-H 13-H 10-H 11-H)13C-NMR (400MHz DMSO-d

6) 17890 15458 15452

14318 13404 13247 13178 13168 13143 12962 12659

Journal of Chemistry 3

12498 12287 11684 11498 Anal Calc C 5028 H 248Found C 5024 H 250

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one (3c) Yield 87 Mp 202ndash204∘C FT-IR (KBrcmminus1) 1666 (C=O) 1610 (C=C) 1H-NMR (400MHzDMSO-d

6) ppm 878 (s 1H 5-H) 837ndash827 (m 13-H 15-H

17-H) 813 (s 1H 7-H) 808 (d 1H 119869 = 156Hz 11-H) 792(d 1H 119869 = 16Hz 10-H) 778ndash768 (m 3H 3-H 2-H 16-H)13C-NMR (400MHz DMSO-d

6) 17873 15467 15440

14895 14186 13666 13570 13187 13092 12957 1265912543 12488 12351 11685 11539 11493 Anal Calc C5486 H 271 N 376 Found C 5490 H 276 N 375

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-[4-(dimethylamino)-phenyl]prop-2-en-1-one (3d) Yield 70 Mp 179ndash181∘CFT-IR (KBr cmminus1) 1646 (C=O) 1579 (C=C) 1H-NMR(400MHz DMSO-d

6) ppm 810 (s 2H 5-H 7-H) 778ndash756

(m 6H 3-H 2-H 13-H 17-H 10-H 11-H) 677 (d 1H119869 = 28Hz 14-H) 675 (d 1H 119869 = 36Hz 16-H) 302 (s6H CH

3) 13C-NMR (400MHz DMSO-d

6) 17852 15535

15431 15275 14569 13161 13110 12985 12624 1220011664 11598 11483 11298 11222 4056ndash3931 Anal Calc C 6164 H 436 N 378 Found C 6140 H 331 N380

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(2-furyl)prop-2-en-1-one (3e)Yield 83Mp 170ndash172∘C FT-IR (KBr cmminus1) 1658(C=O) 1596 (C=C) 1H-NMR (400MHz DMSO-d

6) ppm

803ndash796 (m 3H 5-H 7-H 15-H) 774ndash762 (m 3H 3-H2-H 11-H) 755ndash740 (d 1H 119869 = 152Hz 10-H) 714 (s 1H13-H) 671 (s 1H 14-H) 13C-NMR (400MHz DMSO-d

6)

17856 15454 15441 15134 14715 13148 13078 1296512637 11873 11850 11672 11485 11457 11377 Anal Calc C 5681 H 286 Found C 5675 H 290

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(2-thienyl)prop-2-en-1-one (3f ) Yield 83 Mp 168ndash170∘C FT-IR (KBr cmminus1)1660 (C=O) 1602 (C=C) 1H-NMR (400MHz DMSO-d

6)

ppm 817 (s 1H 5-H) 809 (s 1H 7-H) 802 (d 1H 119869 = 15611-H) 791ndash767 (m 4H 3-H 2-H 15-H and 13-H) 751 (d 1H119869 = 152Hz 10-H) 723 (dd 1H 14-H) 13C-NMR (400MHzDMSO-d

6) 17854 15453 15448 13986 13727 13410

13164 13154 12969 12936 12642 12035 11676 1149011405 Anal Calc C 5681 H 286 Found C 5675 H290

23 In Vitro Antitumor Activity

231 Cell Culture The cell lines of human breast cancer(MCF-7) and human prostate cancer (PC-3) were employedin our study The PC-3 and MCF-7 cell lines were retrievedfromAmericanTypeCultureCollection (ATCC)MCF-7 andPC-3 cells were fed with DMEM medium (supplementedwith 4500mgL glucose 10 FBS 100UmL penicillin and01mgmL streptomycin added) in 75 cm2 culture flasksand RPMI-1640 medium (supplemented 10 FBS 100UmLpenicillin and 01mgmL streptomycin added) respectivelyA humidified carbon dioxide incubator (5 CO

2+ 95 O

2

Panasonic Japan) was used to keep all cells at 37∘Cduring theexperiments Before the treatment of chalcone compoundsthe viability ratios of the cells were identified by 04 trypanblue If the viability ratios were under 90 we did not initiatethe experiments [36]

232 MTT Assay The synthetic chalcone derivatives weretested for their antitumor activities against different typecancer cell lines (PC-3 and MCF-7) using 3-(45-dimethyl-thiazolndash2-yl)-25-diphenyl tetrazolium bromide (MTT) assaymethod The pale-yellow tetrazolium salt MTT was trans-formed by active mitochondria to form a dark blue formazanthat was determined by a microplate reader [37] The MTTmethod provides a simple way to detect living and growingcells without using radioactivity

When the cells were confluent they were removed fromthe flasks using trypsin-EDTA solution and were seeded in96-well plates such that there were 15 times 103 cells in each wellThe plates were incubated for 24 h at 37∘C After treatmentof these cancer cells with DMSO (for positive control group)and different concentrations (1 5 25 50 and 100120583M) ofchalcone compounds (D1 3andashj) in DMSO the cells thenwere incubated for 24 h at 37∘C in 5 CO

2humidified

incubator MTT solution (05mgmL) was prepared from theMTT stock solution in sterile PBS and was added to eachwell and the plates were then incubated for 3 h after theincubation for 24 h with chalcone compounds After thatDMSOand the optical density of the cells were determined byan ELISA reader (Synergy HT USA) at 550 nm wavelengthThe averages of the absorbance values were recorded byreading the control wells that were considered as 100 Thevalues of absorbance achieved from chalcone compoundsand solvent (DMSO) added wells were proportioned to thecontrol values and the percentages of cell viability weredeterminedThe tests were reiterated ten times at several days[38]

24 Statistical Analyses Quantitative data are expressed asmean plusmn standard deviation (SD) Normal distribution wasconfirmed using Kolmogorov-Smirnov test Quantitativedata were analyzed using Kruskal-Wallis 119867 test followingMann-Whitney 119880 test with Bonferroni adjustment as a posthoc test All 119901 values lt 005 were considered as statisticallysignificant All analyses were done by IBMSPSS Statistics 220for Windows The log IC

50values were determined by using

cell viability values of compounds by GraphPad Prism 6program

3 Results and Discussion

The new 1-(5-bromo-1-benzofuran-2-yl)ethanone wasobtained from the reaction of 5-bromosalicylaldehyde and 1-chloroacetone A series of chalcones (3andashf) were synthesizedby condensation of 1-(5-bromo-1-benzofuran-2-yl)ethanoneand various aromatic aldehydes (2andashf) (Scheme 2) For thesynthesis of chalcones the most common route is the base-catalyzed Claisen-Schmidt reaction involving condensation

4 Journal of Chemistry

O

OH

(i)

O

O

CHO(ii)

O

O

R1

R1R1

R2

R2

R3

R3

CH3

D1

ClCH2COCH3

3andashj

Scheme 2 General synthesis of benzofuran ketone (D1) with chalcone derivatives (3andashj) Reagents and conditions (i) K2CO3 acetone reflax

(ii) NaOH MeOH rt

of a benzaldehyde derivative with an acetophenone derivativein methanol with sodium hydroxide catalyst [39ndash41]

The benzofuran substituted chalcone derivatives (3andashf)were characterized by elemental analysis FT-IR 1H and 13C-NMR spectroscopy techniques

Anticancer activity against MCF-7 and PC-3 was investi-gated in both these newly synthesized chalcones (3andashf) andpreviously synthesized chalcone derivatives (3gndashj)

31 Structural Characterization In the FT-IR spectra of 1-(5-bromo-1-benzofuran-2-yl)ethanone C=O stretching vibra-tion was observed at 1667 cmminus1 The synthetic chalcones 3andashf showed characteristic bands between 1646 and 1666 cmminus1(C=O stretching at chalcone) and between 1579 and 1610 cmminus1(C=C stretching at chalcone)

The most characteristic signals in 1H-NMR spectra ofthe benzofuran substituted chalcones were observed at 829ndash803 ppm (B3-H at benzofuran ring) and at 780ndash740 ppm (120572-H and 120573-H of chalcone moiety) with a coupling constantabout 15Hzwhich characterized the transconfiguration of thealkene moiety The signal of 120573-H was found downfield at alower field than that of 120572-H due to resonance of 120587-electronsbetween 120572-carbons and 120573-carbons with carbonyl group Thecarbonyl carbon was observed at about 178 ppm in the 13C-NMR spectra of 3andashf

32 Anticancer Activity The benzofuran substituted chal-cone compounds synthesized were tested for their in vitroanticancer activity against two cancer cell lines includingMCF-7 and PC-3 at five different concentrations (1 5 2550 and 100 120583M) by MTT assay The cell viability percentagesof tested benzofuran substituted chalcone compounds were

Table 1 Evaluation of the cytotoxicity and log IC50

values (120583M)of chalcone compounds and docetaxel (reference chemotherapeuticdrug) of two cancer cell lines log IC

50is the concentration of drug

that reduces cell growth by 50

Compound MCF-7 PC-3log IC

50(120583M) log IC

50(120583M)

D1 212 1543a 189 1673b 145 1243c 501 6313d 579 1813e 042 0673f 230 2473g 443 6113h 255 2573i 628 6303j minus021 092Docetaxel (reference drug) minus048 minus052

determined Figures 1 and 2 show the effects of the benzofu-ran substituted chalcones on cell viability measured at 24 hafter exposure

log IC50

values of compounds 3andashj were calculated byusing inhibition percentage values by GraphPad Prism 6program on a computer log IC

50results of this compound are

given in Table 1The benzofuran substituted chalcones showed anticancer

activity on PC-3 and MCF-7 cell lines (119901 lt 005) All thecompounds at 100120583M concentrations significantly reducedthe viability percentage of PC-3 andMCF-7 cells (119901 lt 0001)

Journal of Chemistry 5

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Con

trol

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25120583

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trol

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trol

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trol

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trol

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trol

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M

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

MCF

-7ce

ll vi

abili

ty (

)M

CF-7

cell

viab

ility

()

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

lowastlowast

lowastlowast

lowast

lowast

lowast

lowastlowastlowast

lowast

lowast

lowast lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

Figure 1 The relative cell viability () of MCF-7 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Structure activity relationships between these chalconederivatives and startingmaterial (D1) demonstrated that ben-zofuran substituted chalcones showed more potent activitiesthan the starting material bearing only an unsubstitutedbenzofuran ring

Among the synthesized chalcones compounds 3a 3hand 3i were found to be the most potent against MCF-7and PC-3 cell lines In general chalcone derivatives showanticancer activity We have not run across any study inliterature on the synthesis and anticancer properties of

6 Journal of Chemistry

PC-3

cell

viab

ility

()

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PC-3

cell

viab

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PC-3

cell

viab

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()

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PC-3

cell

viab

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()

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PC-3

cell

viab

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()

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PC-3

cell

viab

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()

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0

PC-3

cell

viab

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()120

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PC-3

cell

viab

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()

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PC-3

cell

viab

ility

()

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PC-3

cell

viab

ility

()

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PC-3

cell

viab

ility

()

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trol

1120583

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Con

trol

1120583

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100120583

M

lowast

lowast

lowastlowast

lowast

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lowastlowast

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lowastlowast lowastlowastlowastlowast

lowastlowast

lowastlowast

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lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

Figure 2 The relative cell viability () of PC-3 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Journal of Chemistry 7

the chalcone compounds containing benzofuran ring In thisstudy we have firstly synthesized the chalcone compoundscontaining benzofuran ring And also we have firstly studiedon the anticancer properties of these compounds We havestudied only MCF-7 and PC-3 cells These results suggestedthat benzofuran substituted chalcones could be used as leadcompounds to develop novel potent anticancer agents

4 Conclusions

Synthetic benzofuran chalcone compounds were evaluatedin vitro for their anticancer activity by MTT assay Thebenzofuran substituted chalcone derivatives showed highantitumor activity against MCF-7 and PC-3 cell lines (119901 lt0001) These results displayed that chalcone derivativesbearing benzofuran ring may be useful in the future foranticancer drug development

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

The authors thank Fırat University for financial support ofthis work

References

[1] Y-L Chen S-Z Lin J-Y Chang et al ldquoIn vitro and in vivostudies of a novel potential anticancer agent of isochaihulactoneon human lung cancer A549 cellsrdquo Biochemical Pharmacologyvol 72 no 3 pp 308ndash319 2006

[2] R Abonia D Insuasty J Castillo et al ldquoSynthesis of novelquinoline-2-one based chalcones of potential anti-tumor activ-ityrdquo European Journal ofMedicinal Chemistry vol 57 pp 29ndash402012

[3] B-Z Ahn and D-E Sok ldquoMichael acceptors as a tool foranticancer drug designrdquo Current Pharmaceutical Design vol 2no 3 pp 247ndash262 1996

[4] Z Nowakowska ldquoA review of anti-infective and anti-infla-mmatory chalconesrdquo European Journal of Medicinal Chemistryvol 42 no 2 pp 125ndash137 2007

[5] X-W Zhang D-H Zhao Y-C Quan L-P Sun X-M Yinand L-P Guan ldquoSynthesis and evaluation of antiinflammatoryactivity of substituted chalcone derivativesrdquo Medicinal Chem-istry Research vol 19 no 4 pp 403ndash412 2010

[6] H Iqbal V Prabhakar A Sangith B Chandrika and RBalasubramanian ldquoSynthesis anti-inflammatory and antioxi-dant activity of ring-a-monosubstituted chalcone derivativesrdquoMedicinal Chemistry Research vol 23 no 10 pp 4383ndash43942014

[7] M Wan L Xu L Hua et al ldquoSynthesis and evaluation of novelisoxazolyl chalcones as potential anticancer agentsrdquo BioorganicChemistry vol 54 pp 38ndash43 2014

[8] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoAntimalarial activity and synthesis of new trisubstitutedpyrimidinesrdquo Bioorganic and Medicinal Chemistry Letters vol15 no 12 pp 3130ndash3132 2005

[9] M L Go X Wu and X L Liu ldquoChalcones an update oncytotoxic and chemoprotective propertiesrdquo Current MedicinalChemistry vol 12 no 4 pp 483ndash499 2005

[10] P M Sivakumar S Ganesan P Veluchamy and M DobleldquoNovel chalcones and 135-triphenyl-2-pyrazoline derivativesas antibacterial agentsrdquo Chemical Biology amp Drug Design vol76 no 5 pp 407ndash411 2010

[11] H Adibi J S Mojarrad H Asgharloo and G Zarrini ldquoSynthe-sis in vitro antimicrobial and antioxidant activities of chalconeand flavone derivatives holding allylic substitutionsrdquoMedicinalChemistry Research vol 20 no 8 pp 1318ndash1324 2011

[12] K Parikh and D Joshi ldquoAntibacterial and antifungal screeningof newly synthesized benzimidazole-clubbed chalcone deriva-tivesrdquo Medicinal Chemistry Research vol 22 no 8 pp 3688ndash3697 2013

[13] J C Aponte M Verastegui E Malaga et al ldquoSynthesis cyto-toxicity and anti-Trypanosoma cruzi activity of new chalconesrdquoJournal of Medicinal Chemistry vol 51 no 19 pp 6230ndash62342008

[14] A Shah A M Khan R Qureshi F L Ansari M F Nazar andS S Shah ldquoRedox behavior of anticancer chalcone on a glassycarbon electrode and evaluation of its interaction parameterswith DNArdquo International Journal of Molecular Sciences vol 9no 8 pp 1424ndash1434 2008

[15] J Quintin J Desrivot S Thoret P L Menez T Cresteil andG Lewin ldquoSynthesis and biological evaluation of a series oftangeretin-derived chalconesrdquo Bioorganic amp Medicinal Chem-istry Letters vol 19 no 1 pp 167ndash169 2009

[16] S N Mokale P N Dube S A Bhavale et al ldquoSynthesis in-vitro screening and docking analysis of novel pyrrolidine andpiperidine-substituted ethoxy chalcone as anticancer agentsrdquoMedicinal Chemistry Research vol 24 no 5 pp 1842ndash18562015

[17] M Maggiolini G Statti A Vivacqua et al ldquoEstrogenic andantiproliferative activities of isoliquiritigenin in MCF7 breastcancer cellsrdquoThe Journal of Steroid Biochemistry and MolecularBiology vol 82 no 4-5 pp 315ndash322 2002

[18] T Sakai R N Eskander Y Guo et al ldquoFlavokawain B a kavachalcone induces apoptosis in synovial sarcoma cell linesrdquoJournal of Orthopaedic Research vol 30 no 7 pp 1045ndash10502012

[19] S K Kumar E Hager C Pettit H Gurulingappa N EDavidson and S R Khan ldquoDesign synthesis and evaluationof novel boronic-chalcone derivatives as antitumor agentsrdquoJournal of Medicinal Chemistry vol 46 no 14 pp 2813ndash28152003

[20] B Srinivasan T E Johnson R Lad and C Xing ldquoStructuremdashactivity relationship studies of chalcone leading to 3-hydroxy-4310158404101584051015840-tetramethoxychalcone and its analogues as potentnuclear factor 120581B inhibitors and their anticancer activitiesrdquoJournal of Medicinal Chemistry vol 52 no 22 pp 7228ndash72352009

[21] D Kumar N M Kumar K Akamatsu E Kusaka H Haradaand T Ito ldquoSynthesis and biological evaluation of indolyl chal-cones as antitumor agentsrdquo Bioorganic amp Medicinal ChemistryLetters vol 20 no 13 pp 3916ndash3919 2010

[22] S-H Kim E Lee K H Baek et al ldquoChalcones inhibitors fortopoisomerase i and cathepsin B and L as potential anti-canceragentsrdquo Bioorganic and Medicinal Chemistry Letters vol 23 no11 pp 3320ndash3324 2013

[23] H-J Zhang Y Qian D-D Zhu X-G Yang and H-L ZhuldquoSynthesis molecular modeling and biological evaluation of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

2 Journal of Chemistry

O

O

O

O

X1

23

4

5 67 8 9 10

1112

1314

15

1617

1

23

4

5 67 8 9 10

11

12

13 14

15R1

R1R2

R3

3a R1 = Br R2 = H R3 = H

3b R1 = Br R2 = H R3 = Br

3c R1 = Br R2 = NO2 R3 = H

3d R1 = Br R2 = H R3 = N(CH3)2

3i R1 = H R2 = H R3 = H

3j R1 = H R2 = H R3 = N(CH3)2

3e R1 = Br X = O

3f R1 = Br X = S

3g R1 = H X = O

3h R1 = H X = S

Scheme 1 Structure of synthetic derivatives 3andash3j

In this study we aimed at designing and synthesizingnew compounds (3andashf) with both benzofuran and chalconeunits in one molecule and examining anticancer activityof this newly synthesized chalcones (3andashf) and previouslysynthesized chalcones [35] (3gndashj) bearing no substituent inthe benzofuran ring as a different series against human breastcancer cell lines (MCF-7) and human prostate cancer cells(PC-3) (Scheme 1)

2 Materials and Methods

21 Materials Chemical agents used in the present studyincluded dimethyl sulfoxide (DMSO Merck Germany)penicillin-streptomycin fetal bovine serum (FBS) andDMEM (Dulbeccorsquos Modified Eagle Medium) Double-distilled water was used at all stages of the experimentsSamples of chalcone compounds for testing were prepared at1 5 25 50 and 100 120583M concentrations

22 Characterization Techniques Melting points were mea-sured using a differential scanning calorimeter (ShimadzuDSC-50) and were uncorrected NMR spectra were deter-mined on a Bruker AC 400 (400MHz) spectrometer withtetramethylsilane (TMS) as the internal standard in DMSO-d6or CDCl

3as solvents FT-Infrared (FT-IR) spectra were

recorded as KBr pellets on a Perkin-Elmer SpectrumOne FT-IR spectrometer

Synthesis of 1-(5-Bromo-1-benzofuran-2-yl)ethanone (D1) Amixture of 4-bromo salicylaldehyde (1 g 497mmol) andpotassium carbonate (069 g 497mmol) in dry acetone(10mL) was stirred at 25∘C for 1 h Reaction mixture wascooled at 0ndash5∘C and then chloroacetone (4mL 497mmol)was added dropwise Reaction mixture was stirred at roomtemperature for ten minutes and then refluxed Progress ofthe reaction was monitored by TLC Upon completion thereaction mixture was poured on crashed iceThe precipitatedsolid was filtered washed with water and dried The product

was crystallized from ethanol (yield 108 gr 91 mp 117ndash119∘C)

FT-IR (KBr cmminus1) 1667 (C=O) 1542 (C=C) 1H-NMR(400MHz DMSO-d

6) ppm 803 (s 1H 5-H) 782 (s 1H 7-

H) 769 (dd 1H 119869 = 86Hz and 119869 = 82Hz 3-H) 765 (d1H 119869 = 88Hz 2-H) 256 (s 3H methyl protons) 13C-NMR(400MHz DMSO-d

6) 18840 15414 15346 13143 12946

12639 11663 11484 11383 2697 Anal Calc C 5024 H295 Found C 5021 H 299

General Procedure for Synthesis of Chalcones (3andashf ) Asolution of 1-(5-bromo-1-benzofuran-2-yl)ethanone (1 g418mmol) and one of the aldehyde derivatives (2andashf418mmol) in MeOH (10mL) was cooled at 0ndash5∘C andthen 6mL of aqueous NaOH (1molL) was added to thissolution and stirred at room temperature for 3 hThe reactionmixture was poured on crushed ice The precipitated solidwas filtered after neutralization with diluted HCl and waswashed several times with water and then driedThe productwas recrystallized from ethanol

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-phenylprop-2-en-1-one(3a) Yield 70 Mp 145ndash147∘C FT-IR (KBr cmminus1) 1655(C=O) 1599 (C=C) 1H-NMR (400MHz DMSO-d

6) ppm

827 (s 1H 5-H) 812 (s 1H 7-H) 792ndash784 (m 4H 13-H17-H 10-H 11-H) 784ndash765 (m 2H 3-H 2-H) 765ndash740 (m3H 16-H 15-H 14-H) 13C-NMR (400MHz DMSO-d

6)

17896 15459 15455 14446 13476 13163 13146 1296412950 12946 12649 12218 11677 11488 11456 Anal Calc C 6241 H 339 Found C 6243 H 343

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(3-bromophenyl)prop-2-en-1-one (3b) Yield 82 Mp 206ndash208∘C FT-IR (KBrcmminus1) 1654 (C=O) 1604 (C=C) 1H-NMR (400MHzDMSO-d

6) ppm 829 (s 1H 5-H) 815 (s 1H 7-H) 800ndash

762 (m 8H 3-H 2-H 17-H 16-H 14-H 13-H 10-H 11-H)13C-NMR (400MHz DMSO-d

6) 17890 15458 15452

14318 13404 13247 13178 13168 13143 12962 12659

Journal of Chemistry 3

12498 12287 11684 11498 Anal Calc C 5028 H 248Found C 5024 H 250

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one (3c) Yield 87 Mp 202ndash204∘C FT-IR (KBrcmminus1) 1666 (C=O) 1610 (C=C) 1H-NMR (400MHzDMSO-d

6) ppm 878 (s 1H 5-H) 837ndash827 (m 13-H 15-H

17-H) 813 (s 1H 7-H) 808 (d 1H 119869 = 156Hz 11-H) 792(d 1H 119869 = 16Hz 10-H) 778ndash768 (m 3H 3-H 2-H 16-H)13C-NMR (400MHz DMSO-d

6) 17873 15467 15440

14895 14186 13666 13570 13187 13092 12957 1265912543 12488 12351 11685 11539 11493 Anal Calc C5486 H 271 N 376 Found C 5490 H 276 N 375

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-[4-(dimethylamino)-phenyl]prop-2-en-1-one (3d) Yield 70 Mp 179ndash181∘CFT-IR (KBr cmminus1) 1646 (C=O) 1579 (C=C) 1H-NMR(400MHz DMSO-d

6) ppm 810 (s 2H 5-H 7-H) 778ndash756

(m 6H 3-H 2-H 13-H 17-H 10-H 11-H) 677 (d 1H119869 = 28Hz 14-H) 675 (d 1H 119869 = 36Hz 16-H) 302 (s6H CH

3) 13C-NMR (400MHz DMSO-d

6) 17852 15535

15431 15275 14569 13161 13110 12985 12624 1220011664 11598 11483 11298 11222 4056ndash3931 Anal Calc C 6164 H 436 N 378 Found C 6140 H 331 N380

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(2-furyl)prop-2-en-1-one (3e)Yield 83Mp 170ndash172∘C FT-IR (KBr cmminus1) 1658(C=O) 1596 (C=C) 1H-NMR (400MHz DMSO-d

6) ppm

803ndash796 (m 3H 5-H 7-H 15-H) 774ndash762 (m 3H 3-H2-H 11-H) 755ndash740 (d 1H 119869 = 152Hz 10-H) 714 (s 1H13-H) 671 (s 1H 14-H) 13C-NMR (400MHz DMSO-d

6)

17856 15454 15441 15134 14715 13148 13078 1296512637 11873 11850 11672 11485 11457 11377 Anal Calc C 5681 H 286 Found C 5675 H 290

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(2-thienyl)prop-2-en-1-one (3f ) Yield 83 Mp 168ndash170∘C FT-IR (KBr cmminus1)1660 (C=O) 1602 (C=C) 1H-NMR (400MHz DMSO-d

6)

ppm 817 (s 1H 5-H) 809 (s 1H 7-H) 802 (d 1H 119869 = 15611-H) 791ndash767 (m 4H 3-H 2-H 15-H and 13-H) 751 (d 1H119869 = 152Hz 10-H) 723 (dd 1H 14-H) 13C-NMR (400MHzDMSO-d

6) 17854 15453 15448 13986 13727 13410

13164 13154 12969 12936 12642 12035 11676 1149011405 Anal Calc C 5681 H 286 Found C 5675 H290

23 In Vitro Antitumor Activity

231 Cell Culture The cell lines of human breast cancer(MCF-7) and human prostate cancer (PC-3) were employedin our study The PC-3 and MCF-7 cell lines were retrievedfromAmericanTypeCultureCollection (ATCC)MCF-7 andPC-3 cells were fed with DMEM medium (supplementedwith 4500mgL glucose 10 FBS 100UmL penicillin and01mgmL streptomycin added) in 75 cm2 culture flasksand RPMI-1640 medium (supplemented 10 FBS 100UmLpenicillin and 01mgmL streptomycin added) respectivelyA humidified carbon dioxide incubator (5 CO

2+ 95 O

2

Panasonic Japan) was used to keep all cells at 37∘Cduring theexperiments Before the treatment of chalcone compoundsthe viability ratios of the cells were identified by 04 trypanblue If the viability ratios were under 90 we did not initiatethe experiments [36]

232 MTT Assay The synthetic chalcone derivatives weretested for their antitumor activities against different typecancer cell lines (PC-3 and MCF-7) using 3-(45-dimethyl-thiazolndash2-yl)-25-diphenyl tetrazolium bromide (MTT) assaymethod The pale-yellow tetrazolium salt MTT was trans-formed by active mitochondria to form a dark blue formazanthat was determined by a microplate reader [37] The MTTmethod provides a simple way to detect living and growingcells without using radioactivity

When the cells were confluent they were removed fromthe flasks using trypsin-EDTA solution and were seeded in96-well plates such that there were 15 times 103 cells in each wellThe plates were incubated for 24 h at 37∘C After treatmentof these cancer cells with DMSO (for positive control group)and different concentrations (1 5 25 50 and 100120583M) ofchalcone compounds (D1 3andashj) in DMSO the cells thenwere incubated for 24 h at 37∘C in 5 CO

2humidified

incubator MTT solution (05mgmL) was prepared from theMTT stock solution in sterile PBS and was added to eachwell and the plates were then incubated for 3 h after theincubation for 24 h with chalcone compounds After thatDMSOand the optical density of the cells were determined byan ELISA reader (Synergy HT USA) at 550 nm wavelengthThe averages of the absorbance values were recorded byreading the control wells that were considered as 100 Thevalues of absorbance achieved from chalcone compoundsand solvent (DMSO) added wells were proportioned to thecontrol values and the percentages of cell viability weredeterminedThe tests were reiterated ten times at several days[38]

24 Statistical Analyses Quantitative data are expressed asmean plusmn standard deviation (SD) Normal distribution wasconfirmed using Kolmogorov-Smirnov test Quantitativedata were analyzed using Kruskal-Wallis 119867 test followingMann-Whitney 119880 test with Bonferroni adjustment as a posthoc test All 119901 values lt 005 were considered as statisticallysignificant All analyses were done by IBMSPSS Statistics 220for Windows The log IC

50values were determined by using

cell viability values of compounds by GraphPad Prism 6program

3 Results and Discussion

The new 1-(5-bromo-1-benzofuran-2-yl)ethanone wasobtained from the reaction of 5-bromosalicylaldehyde and 1-chloroacetone A series of chalcones (3andashf) were synthesizedby condensation of 1-(5-bromo-1-benzofuran-2-yl)ethanoneand various aromatic aldehydes (2andashf) (Scheme 2) For thesynthesis of chalcones the most common route is the base-catalyzed Claisen-Schmidt reaction involving condensation

4 Journal of Chemistry

O

OH

(i)

O

O

CHO(ii)

O

O

R1

R1R1

R2

R2

R3

R3

CH3

D1

ClCH2COCH3

3andashj

Scheme 2 General synthesis of benzofuran ketone (D1) with chalcone derivatives (3andashj) Reagents and conditions (i) K2CO3 acetone reflax

(ii) NaOH MeOH rt

of a benzaldehyde derivative with an acetophenone derivativein methanol with sodium hydroxide catalyst [39ndash41]

The benzofuran substituted chalcone derivatives (3andashf)were characterized by elemental analysis FT-IR 1H and 13C-NMR spectroscopy techniques

Anticancer activity against MCF-7 and PC-3 was investi-gated in both these newly synthesized chalcones (3andashf) andpreviously synthesized chalcone derivatives (3gndashj)

31 Structural Characterization In the FT-IR spectra of 1-(5-bromo-1-benzofuran-2-yl)ethanone C=O stretching vibra-tion was observed at 1667 cmminus1 The synthetic chalcones 3andashf showed characteristic bands between 1646 and 1666 cmminus1(C=O stretching at chalcone) and between 1579 and 1610 cmminus1(C=C stretching at chalcone)

The most characteristic signals in 1H-NMR spectra ofthe benzofuran substituted chalcones were observed at 829ndash803 ppm (B3-H at benzofuran ring) and at 780ndash740 ppm (120572-H and 120573-H of chalcone moiety) with a coupling constantabout 15Hzwhich characterized the transconfiguration of thealkene moiety The signal of 120573-H was found downfield at alower field than that of 120572-H due to resonance of 120587-electronsbetween 120572-carbons and 120573-carbons with carbonyl group Thecarbonyl carbon was observed at about 178 ppm in the 13C-NMR spectra of 3andashf

32 Anticancer Activity The benzofuran substituted chal-cone compounds synthesized were tested for their in vitroanticancer activity against two cancer cell lines includingMCF-7 and PC-3 at five different concentrations (1 5 2550 and 100 120583M) by MTT assay The cell viability percentagesof tested benzofuran substituted chalcone compounds were

Table 1 Evaluation of the cytotoxicity and log IC50

values (120583M)of chalcone compounds and docetaxel (reference chemotherapeuticdrug) of two cancer cell lines log IC

50is the concentration of drug

that reduces cell growth by 50

Compound MCF-7 PC-3log IC

50(120583M) log IC

50(120583M)

D1 212 1543a 189 1673b 145 1243c 501 6313d 579 1813e 042 0673f 230 2473g 443 6113h 255 2573i 628 6303j minus021 092Docetaxel (reference drug) minus048 minus052

determined Figures 1 and 2 show the effects of the benzofu-ran substituted chalcones on cell viability measured at 24 hafter exposure

log IC50

values of compounds 3andashj were calculated byusing inhibition percentage values by GraphPad Prism 6program on a computer log IC

50results of this compound are

given in Table 1The benzofuran substituted chalcones showed anticancer

activity on PC-3 and MCF-7 cell lines (119901 lt 005) All thecompounds at 100120583M concentrations significantly reducedthe viability percentage of PC-3 andMCF-7 cells (119901 lt 0001)

Journal of Chemistry 5

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

MCF

-7ce

ll vi

abili

ty (

)M

CF-7

cell

viab

ility

()

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

lowastlowast

lowastlowast

lowast

lowast

lowast

lowastlowastlowast

lowast

lowast

lowast lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

Figure 1 The relative cell viability () of MCF-7 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Structure activity relationships between these chalconederivatives and startingmaterial (D1) demonstrated that ben-zofuran substituted chalcones showed more potent activitiesthan the starting material bearing only an unsubstitutedbenzofuran ring

Among the synthesized chalcones compounds 3a 3hand 3i were found to be the most potent against MCF-7and PC-3 cell lines In general chalcone derivatives showanticancer activity We have not run across any study inliterature on the synthesis and anticancer properties of

6 Journal of Chemistry

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

lowast

lowast

lowastlowast

lowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

Figure 2 The relative cell viability () of PC-3 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Journal of Chemistry 7

the chalcone compounds containing benzofuran ring In thisstudy we have firstly synthesized the chalcone compoundscontaining benzofuran ring And also we have firstly studiedon the anticancer properties of these compounds We havestudied only MCF-7 and PC-3 cells These results suggestedthat benzofuran substituted chalcones could be used as leadcompounds to develop novel potent anticancer agents

4 Conclusions

Synthetic benzofuran chalcone compounds were evaluatedin vitro for their anticancer activity by MTT assay Thebenzofuran substituted chalcone derivatives showed highantitumor activity against MCF-7 and PC-3 cell lines (119901 lt0001) These results displayed that chalcone derivativesbearing benzofuran ring may be useful in the future foranticancer drug development

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

The authors thank Fırat University for financial support ofthis work

References

[1] Y-L Chen S-Z Lin J-Y Chang et al ldquoIn vitro and in vivostudies of a novel potential anticancer agent of isochaihulactoneon human lung cancer A549 cellsrdquo Biochemical Pharmacologyvol 72 no 3 pp 308ndash319 2006

[2] R Abonia D Insuasty J Castillo et al ldquoSynthesis of novelquinoline-2-one based chalcones of potential anti-tumor activ-ityrdquo European Journal ofMedicinal Chemistry vol 57 pp 29ndash402012

[3] B-Z Ahn and D-E Sok ldquoMichael acceptors as a tool foranticancer drug designrdquo Current Pharmaceutical Design vol 2no 3 pp 247ndash262 1996

[4] Z Nowakowska ldquoA review of anti-infective and anti-infla-mmatory chalconesrdquo European Journal of Medicinal Chemistryvol 42 no 2 pp 125ndash137 2007

[5] X-W Zhang D-H Zhao Y-C Quan L-P Sun X-M Yinand L-P Guan ldquoSynthesis and evaluation of antiinflammatoryactivity of substituted chalcone derivativesrdquo Medicinal Chem-istry Research vol 19 no 4 pp 403ndash412 2010

[6] H Iqbal V Prabhakar A Sangith B Chandrika and RBalasubramanian ldquoSynthesis anti-inflammatory and antioxi-dant activity of ring-a-monosubstituted chalcone derivativesrdquoMedicinal Chemistry Research vol 23 no 10 pp 4383ndash43942014

[7] M Wan L Xu L Hua et al ldquoSynthesis and evaluation of novelisoxazolyl chalcones as potential anticancer agentsrdquo BioorganicChemistry vol 54 pp 38ndash43 2014

[8] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoAntimalarial activity and synthesis of new trisubstitutedpyrimidinesrdquo Bioorganic and Medicinal Chemistry Letters vol15 no 12 pp 3130ndash3132 2005

[9] M L Go X Wu and X L Liu ldquoChalcones an update oncytotoxic and chemoprotective propertiesrdquo Current MedicinalChemistry vol 12 no 4 pp 483ndash499 2005

[10] P M Sivakumar S Ganesan P Veluchamy and M DobleldquoNovel chalcones and 135-triphenyl-2-pyrazoline derivativesas antibacterial agentsrdquo Chemical Biology amp Drug Design vol76 no 5 pp 407ndash411 2010

[11] H Adibi J S Mojarrad H Asgharloo and G Zarrini ldquoSynthe-sis in vitro antimicrobial and antioxidant activities of chalconeand flavone derivatives holding allylic substitutionsrdquoMedicinalChemistry Research vol 20 no 8 pp 1318ndash1324 2011

[12] K Parikh and D Joshi ldquoAntibacterial and antifungal screeningof newly synthesized benzimidazole-clubbed chalcone deriva-tivesrdquo Medicinal Chemistry Research vol 22 no 8 pp 3688ndash3697 2013

[13] J C Aponte M Verastegui E Malaga et al ldquoSynthesis cyto-toxicity and anti-Trypanosoma cruzi activity of new chalconesrdquoJournal of Medicinal Chemistry vol 51 no 19 pp 6230ndash62342008

[14] A Shah A M Khan R Qureshi F L Ansari M F Nazar andS S Shah ldquoRedox behavior of anticancer chalcone on a glassycarbon electrode and evaluation of its interaction parameterswith DNArdquo International Journal of Molecular Sciences vol 9no 8 pp 1424ndash1434 2008

[15] J Quintin J Desrivot S Thoret P L Menez T Cresteil andG Lewin ldquoSynthesis and biological evaluation of a series oftangeretin-derived chalconesrdquo Bioorganic amp Medicinal Chem-istry Letters vol 19 no 1 pp 167ndash169 2009

[16] S N Mokale P N Dube S A Bhavale et al ldquoSynthesis in-vitro screening and docking analysis of novel pyrrolidine andpiperidine-substituted ethoxy chalcone as anticancer agentsrdquoMedicinal Chemistry Research vol 24 no 5 pp 1842ndash18562015

[17] M Maggiolini G Statti A Vivacqua et al ldquoEstrogenic andantiproliferative activities of isoliquiritigenin in MCF7 breastcancer cellsrdquoThe Journal of Steroid Biochemistry and MolecularBiology vol 82 no 4-5 pp 315ndash322 2002

[18] T Sakai R N Eskander Y Guo et al ldquoFlavokawain B a kavachalcone induces apoptosis in synovial sarcoma cell linesrdquoJournal of Orthopaedic Research vol 30 no 7 pp 1045ndash10502012

[19] S K Kumar E Hager C Pettit H Gurulingappa N EDavidson and S R Khan ldquoDesign synthesis and evaluationof novel boronic-chalcone derivatives as antitumor agentsrdquoJournal of Medicinal Chemistry vol 46 no 14 pp 2813ndash28152003

[20] B Srinivasan T E Johnson R Lad and C Xing ldquoStructuremdashactivity relationship studies of chalcone leading to 3-hydroxy-4310158404101584051015840-tetramethoxychalcone and its analogues as potentnuclear factor 120581B inhibitors and their anticancer activitiesrdquoJournal of Medicinal Chemistry vol 52 no 22 pp 7228ndash72352009

[21] D Kumar N M Kumar K Akamatsu E Kusaka H Haradaand T Ito ldquoSynthesis and biological evaluation of indolyl chal-cones as antitumor agentsrdquo Bioorganic amp Medicinal ChemistryLetters vol 20 no 13 pp 3916ndash3919 2010

[22] S-H Kim E Lee K H Baek et al ldquoChalcones inhibitors fortopoisomerase i and cathepsin B and L as potential anti-canceragentsrdquo Bioorganic and Medicinal Chemistry Letters vol 23 no11 pp 3320ndash3324 2013

[23] H-J Zhang Y Qian D-D Zhu X-G Yang and H-L ZhuldquoSynthesis molecular modeling and biological evaluation of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 3

12498 12287 11684 11498 Anal Calc C 5028 H 248Found C 5024 H 250

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(3-nitrophenyl)prop-2-en-1-one (3c) Yield 87 Mp 202ndash204∘C FT-IR (KBrcmminus1) 1666 (C=O) 1610 (C=C) 1H-NMR (400MHzDMSO-d

6) ppm 878 (s 1H 5-H) 837ndash827 (m 13-H 15-H

17-H) 813 (s 1H 7-H) 808 (d 1H 119869 = 156Hz 11-H) 792(d 1H 119869 = 16Hz 10-H) 778ndash768 (m 3H 3-H 2-H 16-H)13C-NMR (400MHz DMSO-d

6) 17873 15467 15440

14895 14186 13666 13570 13187 13092 12957 1265912543 12488 12351 11685 11539 11493 Anal Calc C5486 H 271 N 376 Found C 5490 H 276 N 375

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-[4-(dimethylamino)-phenyl]prop-2-en-1-one (3d) Yield 70 Mp 179ndash181∘CFT-IR (KBr cmminus1) 1646 (C=O) 1579 (C=C) 1H-NMR(400MHz DMSO-d

6) ppm 810 (s 2H 5-H 7-H) 778ndash756

(m 6H 3-H 2-H 13-H 17-H 10-H 11-H) 677 (d 1H119869 = 28Hz 14-H) 675 (d 1H 119869 = 36Hz 16-H) 302 (s6H CH

3) 13C-NMR (400MHz DMSO-d

6) 17852 15535

15431 15275 14569 13161 13110 12985 12624 1220011664 11598 11483 11298 11222 4056ndash3931 Anal Calc C 6164 H 436 N 378 Found C 6140 H 331 N380

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(2-furyl)prop-2-en-1-one (3e)Yield 83Mp 170ndash172∘C FT-IR (KBr cmminus1) 1658(C=O) 1596 (C=C) 1H-NMR (400MHz DMSO-d

6) ppm

803ndash796 (m 3H 5-H 7-H 15-H) 774ndash762 (m 3H 3-H2-H 11-H) 755ndash740 (d 1H 119869 = 152Hz 10-H) 714 (s 1H13-H) 671 (s 1H 14-H) 13C-NMR (400MHz DMSO-d

6)

17856 15454 15441 15134 14715 13148 13078 1296512637 11873 11850 11672 11485 11457 11377 Anal Calc C 5681 H 286 Found C 5675 H 290

(2E)-1-(5-Bromo-1-benzofuran-2-yl)-3-(2-thienyl)prop-2-en-1-one (3f ) Yield 83 Mp 168ndash170∘C FT-IR (KBr cmminus1)1660 (C=O) 1602 (C=C) 1H-NMR (400MHz DMSO-d

6)

ppm 817 (s 1H 5-H) 809 (s 1H 7-H) 802 (d 1H 119869 = 15611-H) 791ndash767 (m 4H 3-H 2-H 15-H and 13-H) 751 (d 1H119869 = 152Hz 10-H) 723 (dd 1H 14-H) 13C-NMR (400MHzDMSO-d

6) 17854 15453 15448 13986 13727 13410

13164 13154 12969 12936 12642 12035 11676 1149011405 Anal Calc C 5681 H 286 Found C 5675 H290

23 In Vitro Antitumor Activity

231 Cell Culture The cell lines of human breast cancer(MCF-7) and human prostate cancer (PC-3) were employedin our study The PC-3 and MCF-7 cell lines were retrievedfromAmericanTypeCultureCollection (ATCC)MCF-7 andPC-3 cells were fed with DMEM medium (supplementedwith 4500mgL glucose 10 FBS 100UmL penicillin and01mgmL streptomycin added) in 75 cm2 culture flasksand RPMI-1640 medium (supplemented 10 FBS 100UmLpenicillin and 01mgmL streptomycin added) respectivelyA humidified carbon dioxide incubator (5 CO

2+ 95 O

2

Panasonic Japan) was used to keep all cells at 37∘Cduring theexperiments Before the treatment of chalcone compoundsthe viability ratios of the cells were identified by 04 trypanblue If the viability ratios were under 90 we did not initiatethe experiments [36]

232 MTT Assay The synthetic chalcone derivatives weretested for their antitumor activities against different typecancer cell lines (PC-3 and MCF-7) using 3-(45-dimethyl-thiazolndash2-yl)-25-diphenyl tetrazolium bromide (MTT) assaymethod The pale-yellow tetrazolium salt MTT was trans-formed by active mitochondria to form a dark blue formazanthat was determined by a microplate reader [37] The MTTmethod provides a simple way to detect living and growingcells without using radioactivity

When the cells were confluent they were removed fromthe flasks using trypsin-EDTA solution and were seeded in96-well plates such that there were 15 times 103 cells in each wellThe plates were incubated for 24 h at 37∘C After treatmentof these cancer cells with DMSO (for positive control group)and different concentrations (1 5 25 50 and 100120583M) ofchalcone compounds (D1 3andashj) in DMSO the cells thenwere incubated for 24 h at 37∘C in 5 CO

2humidified

incubator MTT solution (05mgmL) was prepared from theMTT stock solution in sterile PBS and was added to eachwell and the plates were then incubated for 3 h after theincubation for 24 h with chalcone compounds After thatDMSOand the optical density of the cells were determined byan ELISA reader (Synergy HT USA) at 550 nm wavelengthThe averages of the absorbance values were recorded byreading the control wells that were considered as 100 Thevalues of absorbance achieved from chalcone compoundsand solvent (DMSO) added wells were proportioned to thecontrol values and the percentages of cell viability weredeterminedThe tests were reiterated ten times at several days[38]

24 Statistical Analyses Quantitative data are expressed asmean plusmn standard deviation (SD) Normal distribution wasconfirmed using Kolmogorov-Smirnov test Quantitativedata were analyzed using Kruskal-Wallis 119867 test followingMann-Whitney 119880 test with Bonferroni adjustment as a posthoc test All 119901 values lt 005 were considered as statisticallysignificant All analyses were done by IBMSPSS Statistics 220for Windows The log IC

50values were determined by using

cell viability values of compounds by GraphPad Prism 6program

3 Results and Discussion

The new 1-(5-bromo-1-benzofuran-2-yl)ethanone wasobtained from the reaction of 5-bromosalicylaldehyde and 1-chloroacetone A series of chalcones (3andashf) were synthesizedby condensation of 1-(5-bromo-1-benzofuran-2-yl)ethanoneand various aromatic aldehydes (2andashf) (Scheme 2) For thesynthesis of chalcones the most common route is the base-catalyzed Claisen-Schmidt reaction involving condensation

4 Journal of Chemistry

O

OH

(i)

O

O

CHO(ii)

O

O

R1

R1R1

R2

R2

R3

R3

CH3

D1

ClCH2COCH3

3andashj

Scheme 2 General synthesis of benzofuran ketone (D1) with chalcone derivatives (3andashj) Reagents and conditions (i) K2CO3 acetone reflax

(ii) NaOH MeOH rt

of a benzaldehyde derivative with an acetophenone derivativein methanol with sodium hydroxide catalyst [39ndash41]

The benzofuran substituted chalcone derivatives (3andashf)were characterized by elemental analysis FT-IR 1H and 13C-NMR spectroscopy techniques

Anticancer activity against MCF-7 and PC-3 was investi-gated in both these newly synthesized chalcones (3andashf) andpreviously synthesized chalcone derivatives (3gndashj)

31 Structural Characterization In the FT-IR spectra of 1-(5-bromo-1-benzofuran-2-yl)ethanone C=O stretching vibra-tion was observed at 1667 cmminus1 The synthetic chalcones 3andashf showed characteristic bands between 1646 and 1666 cmminus1(C=O stretching at chalcone) and between 1579 and 1610 cmminus1(C=C stretching at chalcone)

The most characteristic signals in 1H-NMR spectra ofthe benzofuran substituted chalcones were observed at 829ndash803 ppm (B3-H at benzofuran ring) and at 780ndash740 ppm (120572-H and 120573-H of chalcone moiety) with a coupling constantabout 15Hzwhich characterized the transconfiguration of thealkene moiety The signal of 120573-H was found downfield at alower field than that of 120572-H due to resonance of 120587-electronsbetween 120572-carbons and 120573-carbons with carbonyl group Thecarbonyl carbon was observed at about 178 ppm in the 13C-NMR spectra of 3andashf

32 Anticancer Activity The benzofuran substituted chal-cone compounds synthesized were tested for their in vitroanticancer activity against two cancer cell lines includingMCF-7 and PC-3 at five different concentrations (1 5 2550 and 100 120583M) by MTT assay The cell viability percentagesof tested benzofuran substituted chalcone compounds were

Table 1 Evaluation of the cytotoxicity and log IC50

values (120583M)of chalcone compounds and docetaxel (reference chemotherapeuticdrug) of two cancer cell lines log IC

50is the concentration of drug

that reduces cell growth by 50

Compound MCF-7 PC-3log IC

50(120583M) log IC

50(120583M)

D1 212 1543a 189 1673b 145 1243c 501 6313d 579 1813e 042 0673f 230 2473g 443 6113h 255 2573i 628 6303j minus021 092Docetaxel (reference drug) minus048 minus052

determined Figures 1 and 2 show the effects of the benzofu-ran substituted chalcones on cell viability measured at 24 hafter exposure

log IC50

values of compounds 3andashj were calculated byusing inhibition percentage values by GraphPad Prism 6program on a computer log IC

50results of this compound are

given in Table 1The benzofuran substituted chalcones showed anticancer

activity on PC-3 and MCF-7 cell lines (119901 lt 005) All thecompounds at 100120583M concentrations significantly reducedthe viability percentage of PC-3 andMCF-7 cells (119901 lt 0001)

Journal of Chemistry 5

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

MCF

-7ce

ll vi

abili

ty (

)M

CF-7

cell

viab

ility

()

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

lowastlowast

lowastlowast

lowast

lowast

lowast

lowastlowastlowast

lowast

lowast

lowast lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

Figure 1 The relative cell viability () of MCF-7 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Structure activity relationships between these chalconederivatives and startingmaterial (D1) demonstrated that ben-zofuran substituted chalcones showed more potent activitiesthan the starting material bearing only an unsubstitutedbenzofuran ring

Among the synthesized chalcones compounds 3a 3hand 3i were found to be the most potent against MCF-7and PC-3 cell lines In general chalcone derivatives showanticancer activity We have not run across any study inliterature on the synthesis and anticancer properties of

6 Journal of Chemistry

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

lowast

lowast

lowastlowast

lowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

Figure 2 The relative cell viability () of PC-3 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Journal of Chemistry 7

the chalcone compounds containing benzofuran ring In thisstudy we have firstly synthesized the chalcone compoundscontaining benzofuran ring And also we have firstly studiedon the anticancer properties of these compounds We havestudied only MCF-7 and PC-3 cells These results suggestedthat benzofuran substituted chalcones could be used as leadcompounds to develop novel potent anticancer agents

4 Conclusions

Synthetic benzofuran chalcone compounds were evaluatedin vitro for their anticancer activity by MTT assay Thebenzofuran substituted chalcone derivatives showed highantitumor activity against MCF-7 and PC-3 cell lines (119901 lt0001) These results displayed that chalcone derivativesbearing benzofuran ring may be useful in the future foranticancer drug development

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

The authors thank Fırat University for financial support ofthis work

References

[1] Y-L Chen S-Z Lin J-Y Chang et al ldquoIn vitro and in vivostudies of a novel potential anticancer agent of isochaihulactoneon human lung cancer A549 cellsrdquo Biochemical Pharmacologyvol 72 no 3 pp 308ndash319 2006

[2] R Abonia D Insuasty J Castillo et al ldquoSynthesis of novelquinoline-2-one based chalcones of potential anti-tumor activ-ityrdquo European Journal ofMedicinal Chemistry vol 57 pp 29ndash402012

[3] B-Z Ahn and D-E Sok ldquoMichael acceptors as a tool foranticancer drug designrdquo Current Pharmaceutical Design vol 2no 3 pp 247ndash262 1996

[4] Z Nowakowska ldquoA review of anti-infective and anti-infla-mmatory chalconesrdquo European Journal of Medicinal Chemistryvol 42 no 2 pp 125ndash137 2007

[5] X-W Zhang D-H Zhao Y-C Quan L-P Sun X-M Yinand L-P Guan ldquoSynthesis and evaluation of antiinflammatoryactivity of substituted chalcone derivativesrdquo Medicinal Chem-istry Research vol 19 no 4 pp 403ndash412 2010

[6] H Iqbal V Prabhakar A Sangith B Chandrika and RBalasubramanian ldquoSynthesis anti-inflammatory and antioxi-dant activity of ring-a-monosubstituted chalcone derivativesrdquoMedicinal Chemistry Research vol 23 no 10 pp 4383ndash43942014

[7] M Wan L Xu L Hua et al ldquoSynthesis and evaluation of novelisoxazolyl chalcones as potential anticancer agentsrdquo BioorganicChemistry vol 54 pp 38ndash43 2014

[8] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoAntimalarial activity and synthesis of new trisubstitutedpyrimidinesrdquo Bioorganic and Medicinal Chemistry Letters vol15 no 12 pp 3130ndash3132 2005

[9] M L Go X Wu and X L Liu ldquoChalcones an update oncytotoxic and chemoprotective propertiesrdquo Current MedicinalChemistry vol 12 no 4 pp 483ndash499 2005

[10] P M Sivakumar S Ganesan P Veluchamy and M DobleldquoNovel chalcones and 135-triphenyl-2-pyrazoline derivativesas antibacterial agentsrdquo Chemical Biology amp Drug Design vol76 no 5 pp 407ndash411 2010

[11] H Adibi J S Mojarrad H Asgharloo and G Zarrini ldquoSynthe-sis in vitro antimicrobial and antioxidant activities of chalconeand flavone derivatives holding allylic substitutionsrdquoMedicinalChemistry Research vol 20 no 8 pp 1318ndash1324 2011

[12] K Parikh and D Joshi ldquoAntibacterial and antifungal screeningof newly synthesized benzimidazole-clubbed chalcone deriva-tivesrdquo Medicinal Chemistry Research vol 22 no 8 pp 3688ndash3697 2013

[13] J C Aponte M Verastegui E Malaga et al ldquoSynthesis cyto-toxicity and anti-Trypanosoma cruzi activity of new chalconesrdquoJournal of Medicinal Chemistry vol 51 no 19 pp 6230ndash62342008

[14] A Shah A M Khan R Qureshi F L Ansari M F Nazar andS S Shah ldquoRedox behavior of anticancer chalcone on a glassycarbon electrode and evaluation of its interaction parameterswith DNArdquo International Journal of Molecular Sciences vol 9no 8 pp 1424ndash1434 2008

[15] J Quintin J Desrivot S Thoret P L Menez T Cresteil andG Lewin ldquoSynthesis and biological evaluation of a series oftangeretin-derived chalconesrdquo Bioorganic amp Medicinal Chem-istry Letters vol 19 no 1 pp 167ndash169 2009

[16] S N Mokale P N Dube S A Bhavale et al ldquoSynthesis in-vitro screening and docking analysis of novel pyrrolidine andpiperidine-substituted ethoxy chalcone as anticancer agentsrdquoMedicinal Chemistry Research vol 24 no 5 pp 1842ndash18562015

[17] M Maggiolini G Statti A Vivacqua et al ldquoEstrogenic andantiproliferative activities of isoliquiritigenin in MCF7 breastcancer cellsrdquoThe Journal of Steroid Biochemistry and MolecularBiology vol 82 no 4-5 pp 315ndash322 2002

[18] T Sakai R N Eskander Y Guo et al ldquoFlavokawain B a kavachalcone induces apoptosis in synovial sarcoma cell linesrdquoJournal of Orthopaedic Research vol 30 no 7 pp 1045ndash10502012

[19] S K Kumar E Hager C Pettit H Gurulingappa N EDavidson and S R Khan ldquoDesign synthesis and evaluationof novel boronic-chalcone derivatives as antitumor agentsrdquoJournal of Medicinal Chemistry vol 46 no 14 pp 2813ndash28152003

[20] B Srinivasan T E Johnson R Lad and C Xing ldquoStructuremdashactivity relationship studies of chalcone leading to 3-hydroxy-4310158404101584051015840-tetramethoxychalcone and its analogues as potentnuclear factor 120581B inhibitors and their anticancer activitiesrdquoJournal of Medicinal Chemistry vol 52 no 22 pp 7228ndash72352009

[21] D Kumar N M Kumar K Akamatsu E Kusaka H Haradaand T Ito ldquoSynthesis and biological evaluation of indolyl chal-cones as antitumor agentsrdquo Bioorganic amp Medicinal ChemistryLetters vol 20 no 13 pp 3916ndash3919 2010

[22] S-H Kim E Lee K H Baek et al ldquoChalcones inhibitors fortopoisomerase i and cathepsin B and L as potential anti-canceragentsrdquo Bioorganic and Medicinal Chemistry Letters vol 23 no11 pp 3320ndash3324 2013

[23] H-J Zhang Y Qian D-D Zhu X-G Yang and H-L ZhuldquoSynthesis molecular modeling and biological evaluation of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

4 Journal of Chemistry

O

OH

(i)

O

O

CHO(ii)

O

O

R1

R1R1

R2

R2

R3

R3

CH3

D1

ClCH2COCH3

3andashj

Scheme 2 General synthesis of benzofuran ketone (D1) with chalcone derivatives (3andashj) Reagents and conditions (i) K2CO3 acetone reflax

(ii) NaOH MeOH rt

of a benzaldehyde derivative with an acetophenone derivativein methanol with sodium hydroxide catalyst [39ndash41]

The benzofuran substituted chalcone derivatives (3andashf)were characterized by elemental analysis FT-IR 1H and 13C-NMR spectroscopy techniques

Anticancer activity against MCF-7 and PC-3 was investi-gated in both these newly synthesized chalcones (3andashf) andpreviously synthesized chalcone derivatives (3gndashj)

31 Structural Characterization In the FT-IR spectra of 1-(5-bromo-1-benzofuran-2-yl)ethanone C=O stretching vibra-tion was observed at 1667 cmminus1 The synthetic chalcones 3andashf showed characteristic bands between 1646 and 1666 cmminus1(C=O stretching at chalcone) and between 1579 and 1610 cmminus1(C=C stretching at chalcone)

The most characteristic signals in 1H-NMR spectra ofthe benzofuran substituted chalcones were observed at 829ndash803 ppm (B3-H at benzofuran ring) and at 780ndash740 ppm (120572-H and 120573-H of chalcone moiety) with a coupling constantabout 15Hzwhich characterized the transconfiguration of thealkene moiety The signal of 120573-H was found downfield at alower field than that of 120572-H due to resonance of 120587-electronsbetween 120572-carbons and 120573-carbons with carbonyl group Thecarbonyl carbon was observed at about 178 ppm in the 13C-NMR spectra of 3andashf

32 Anticancer Activity The benzofuran substituted chal-cone compounds synthesized were tested for their in vitroanticancer activity against two cancer cell lines includingMCF-7 and PC-3 at five different concentrations (1 5 2550 and 100 120583M) by MTT assay The cell viability percentagesof tested benzofuran substituted chalcone compounds were

Table 1 Evaluation of the cytotoxicity and log IC50

values (120583M)of chalcone compounds and docetaxel (reference chemotherapeuticdrug) of two cancer cell lines log IC

50is the concentration of drug

that reduces cell growth by 50

Compound MCF-7 PC-3log IC

50(120583M) log IC

50(120583M)

D1 212 1543a 189 1673b 145 1243c 501 6313d 579 1813e 042 0673f 230 2473g 443 6113h 255 2573i 628 6303j minus021 092Docetaxel (reference drug) minus048 minus052

determined Figures 1 and 2 show the effects of the benzofu-ran substituted chalcones on cell viability measured at 24 hafter exposure

log IC50

values of compounds 3andashj were calculated byusing inhibition percentage values by GraphPad Prism 6program on a computer log IC

50results of this compound are

given in Table 1The benzofuran substituted chalcones showed anticancer

activity on PC-3 and MCF-7 cell lines (119901 lt 005) All thecompounds at 100120583M concentrations significantly reducedthe viability percentage of PC-3 andMCF-7 cells (119901 lt 0001)

Journal of Chemistry 5

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

MCF

-7ce

ll vi

abili

ty (

)M

CF-7

cell

viab

ility

()

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

lowastlowast

lowastlowast

lowast

lowast

lowast

lowastlowastlowast

lowast

lowast

lowast lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

Figure 1 The relative cell viability () of MCF-7 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Structure activity relationships between these chalconederivatives and startingmaterial (D1) demonstrated that ben-zofuran substituted chalcones showed more potent activitiesthan the starting material bearing only an unsubstitutedbenzofuran ring

Among the synthesized chalcones compounds 3a 3hand 3i were found to be the most potent against MCF-7and PC-3 cell lines In general chalcone derivatives showanticancer activity We have not run across any study inliterature on the synthesis and anticancer properties of

6 Journal of Chemistry

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

lowast

lowast

lowastlowast

lowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

Figure 2 The relative cell viability () of PC-3 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Journal of Chemistry 7

the chalcone compounds containing benzofuran ring In thisstudy we have firstly synthesized the chalcone compoundscontaining benzofuran ring And also we have firstly studiedon the anticancer properties of these compounds We havestudied only MCF-7 and PC-3 cells These results suggestedthat benzofuran substituted chalcones could be used as leadcompounds to develop novel potent anticancer agents

4 Conclusions

Synthetic benzofuran chalcone compounds were evaluatedin vitro for their anticancer activity by MTT assay Thebenzofuran substituted chalcone derivatives showed highantitumor activity against MCF-7 and PC-3 cell lines (119901 lt0001) These results displayed that chalcone derivativesbearing benzofuran ring may be useful in the future foranticancer drug development

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

The authors thank Fırat University for financial support ofthis work

References

[1] Y-L Chen S-Z Lin J-Y Chang et al ldquoIn vitro and in vivostudies of a novel potential anticancer agent of isochaihulactoneon human lung cancer A549 cellsrdquo Biochemical Pharmacologyvol 72 no 3 pp 308ndash319 2006

[2] R Abonia D Insuasty J Castillo et al ldquoSynthesis of novelquinoline-2-one based chalcones of potential anti-tumor activ-ityrdquo European Journal ofMedicinal Chemistry vol 57 pp 29ndash402012

[3] B-Z Ahn and D-E Sok ldquoMichael acceptors as a tool foranticancer drug designrdquo Current Pharmaceutical Design vol 2no 3 pp 247ndash262 1996

[4] Z Nowakowska ldquoA review of anti-infective and anti-infla-mmatory chalconesrdquo European Journal of Medicinal Chemistryvol 42 no 2 pp 125ndash137 2007

[5] X-W Zhang D-H Zhao Y-C Quan L-P Sun X-M Yinand L-P Guan ldquoSynthesis and evaluation of antiinflammatoryactivity of substituted chalcone derivativesrdquo Medicinal Chem-istry Research vol 19 no 4 pp 403ndash412 2010

[6] H Iqbal V Prabhakar A Sangith B Chandrika and RBalasubramanian ldquoSynthesis anti-inflammatory and antioxi-dant activity of ring-a-monosubstituted chalcone derivativesrdquoMedicinal Chemistry Research vol 23 no 10 pp 4383ndash43942014

[7] M Wan L Xu L Hua et al ldquoSynthesis and evaluation of novelisoxazolyl chalcones as potential anticancer agentsrdquo BioorganicChemistry vol 54 pp 38ndash43 2014

[8] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoAntimalarial activity and synthesis of new trisubstitutedpyrimidinesrdquo Bioorganic and Medicinal Chemistry Letters vol15 no 12 pp 3130ndash3132 2005

[9] M L Go X Wu and X L Liu ldquoChalcones an update oncytotoxic and chemoprotective propertiesrdquo Current MedicinalChemistry vol 12 no 4 pp 483ndash499 2005

[10] P M Sivakumar S Ganesan P Veluchamy and M DobleldquoNovel chalcones and 135-triphenyl-2-pyrazoline derivativesas antibacterial agentsrdquo Chemical Biology amp Drug Design vol76 no 5 pp 407ndash411 2010

[11] H Adibi J S Mojarrad H Asgharloo and G Zarrini ldquoSynthe-sis in vitro antimicrobial and antioxidant activities of chalconeand flavone derivatives holding allylic substitutionsrdquoMedicinalChemistry Research vol 20 no 8 pp 1318ndash1324 2011

[12] K Parikh and D Joshi ldquoAntibacterial and antifungal screeningof newly synthesized benzimidazole-clubbed chalcone deriva-tivesrdquo Medicinal Chemistry Research vol 22 no 8 pp 3688ndash3697 2013

[13] J C Aponte M Verastegui E Malaga et al ldquoSynthesis cyto-toxicity and anti-Trypanosoma cruzi activity of new chalconesrdquoJournal of Medicinal Chemistry vol 51 no 19 pp 6230ndash62342008

[14] A Shah A M Khan R Qureshi F L Ansari M F Nazar andS S Shah ldquoRedox behavior of anticancer chalcone on a glassycarbon electrode and evaluation of its interaction parameterswith DNArdquo International Journal of Molecular Sciences vol 9no 8 pp 1424ndash1434 2008

[15] J Quintin J Desrivot S Thoret P L Menez T Cresteil andG Lewin ldquoSynthesis and biological evaluation of a series oftangeretin-derived chalconesrdquo Bioorganic amp Medicinal Chem-istry Letters vol 19 no 1 pp 167ndash169 2009

[16] S N Mokale P N Dube S A Bhavale et al ldquoSynthesis in-vitro screening and docking analysis of novel pyrrolidine andpiperidine-substituted ethoxy chalcone as anticancer agentsrdquoMedicinal Chemistry Research vol 24 no 5 pp 1842ndash18562015

[17] M Maggiolini G Statti A Vivacqua et al ldquoEstrogenic andantiproliferative activities of isoliquiritigenin in MCF7 breastcancer cellsrdquoThe Journal of Steroid Biochemistry and MolecularBiology vol 82 no 4-5 pp 315ndash322 2002

[18] T Sakai R N Eskander Y Guo et al ldquoFlavokawain B a kavachalcone induces apoptosis in synovial sarcoma cell linesrdquoJournal of Orthopaedic Research vol 30 no 7 pp 1045ndash10502012

[19] S K Kumar E Hager C Pettit H Gurulingappa N EDavidson and S R Khan ldquoDesign synthesis and evaluationof novel boronic-chalcone derivatives as antitumor agentsrdquoJournal of Medicinal Chemistry vol 46 no 14 pp 2813ndash28152003

[20] B Srinivasan T E Johnson R Lad and C Xing ldquoStructuremdashactivity relationship studies of chalcone leading to 3-hydroxy-4310158404101584051015840-tetramethoxychalcone and its analogues as potentnuclear factor 120581B inhibitors and their anticancer activitiesrdquoJournal of Medicinal Chemistry vol 52 no 22 pp 7228ndash72352009

[21] D Kumar N M Kumar K Akamatsu E Kusaka H Haradaand T Ito ldquoSynthesis and biological evaluation of indolyl chal-cones as antitumor agentsrdquo Bioorganic amp Medicinal ChemistryLetters vol 20 no 13 pp 3916ndash3919 2010

[22] S-H Kim E Lee K H Baek et al ldquoChalcones inhibitors fortopoisomerase i and cathepsin B and L as potential anti-canceragentsrdquo Bioorganic and Medicinal Chemistry Letters vol 23 no11 pp 3320ndash3324 2013

[23] H-J Zhang Y Qian D-D Zhu X-G Yang and H-L ZhuldquoSynthesis molecular modeling and biological evaluation of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 5

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

MCF

-7ce

ll vi

abili

ty (

)M

CF-7

cell

viab

ility

()

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

MCF

-7ce

ll vi

abili

ty (

)

lowastlowast

lowastlowast

lowast

lowast

lowast

lowastlowastlowast

lowast

lowast

lowast lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

Figure 1 The relative cell viability () of MCF-7 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Structure activity relationships between these chalconederivatives and startingmaterial (D1) demonstrated that ben-zofuran substituted chalcones showed more potent activitiesthan the starting material bearing only an unsubstitutedbenzofuran ring

Among the synthesized chalcones compounds 3a 3hand 3i were found to be the most potent against MCF-7and PC-3 cell lines In general chalcone derivatives showanticancer activity We have not run across any study inliterature on the synthesis and anticancer properties of

6 Journal of Chemistry

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

lowast

lowast

lowastlowast

lowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

Figure 2 The relative cell viability () of PC-3 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Journal of Chemistry 7

the chalcone compounds containing benzofuran ring In thisstudy we have firstly synthesized the chalcone compoundscontaining benzofuran ring And also we have firstly studiedon the anticancer properties of these compounds We havestudied only MCF-7 and PC-3 cells These results suggestedthat benzofuran substituted chalcones could be used as leadcompounds to develop novel potent anticancer agents

4 Conclusions

Synthetic benzofuran chalcone compounds were evaluatedin vitro for their anticancer activity by MTT assay Thebenzofuran substituted chalcone derivatives showed highantitumor activity against MCF-7 and PC-3 cell lines (119901 lt0001) These results displayed that chalcone derivativesbearing benzofuran ring may be useful in the future foranticancer drug development

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

The authors thank Fırat University for financial support ofthis work

References

[1] Y-L Chen S-Z Lin J-Y Chang et al ldquoIn vitro and in vivostudies of a novel potential anticancer agent of isochaihulactoneon human lung cancer A549 cellsrdquo Biochemical Pharmacologyvol 72 no 3 pp 308ndash319 2006

[2] R Abonia D Insuasty J Castillo et al ldquoSynthesis of novelquinoline-2-one based chalcones of potential anti-tumor activ-ityrdquo European Journal ofMedicinal Chemistry vol 57 pp 29ndash402012

[3] B-Z Ahn and D-E Sok ldquoMichael acceptors as a tool foranticancer drug designrdquo Current Pharmaceutical Design vol 2no 3 pp 247ndash262 1996

[4] Z Nowakowska ldquoA review of anti-infective and anti-infla-mmatory chalconesrdquo European Journal of Medicinal Chemistryvol 42 no 2 pp 125ndash137 2007

[5] X-W Zhang D-H Zhao Y-C Quan L-P Sun X-M Yinand L-P Guan ldquoSynthesis and evaluation of antiinflammatoryactivity of substituted chalcone derivativesrdquo Medicinal Chem-istry Research vol 19 no 4 pp 403ndash412 2010

[6] H Iqbal V Prabhakar A Sangith B Chandrika and RBalasubramanian ldquoSynthesis anti-inflammatory and antioxi-dant activity of ring-a-monosubstituted chalcone derivativesrdquoMedicinal Chemistry Research vol 23 no 10 pp 4383ndash43942014

[7] M Wan L Xu L Hua et al ldquoSynthesis and evaluation of novelisoxazolyl chalcones as potential anticancer agentsrdquo BioorganicChemistry vol 54 pp 38ndash43 2014

[8] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoAntimalarial activity and synthesis of new trisubstitutedpyrimidinesrdquo Bioorganic and Medicinal Chemistry Letters vol15 no 12 pp 3130ndash3132 2005

[9] M L Go X Wu and X L Liu ldquoChalcones an update oncytotoxic and chemoprotective propertiesrdquo Current MedicinalChemistry vol 12 no 4 pp 483ndash499 2005

[10] P M Sivakumar S Ganesan P Veluchamy and M DobleldquoNovel chalcones and 135-triphenyl-2-pyrazoline derivativesas antibacterial agentsrdquo Chemical Biology amp Drug Design vol76 no 5 pp 407ndash411 2010

[11] H Adibi J S Mojarrad H Asgharloo and G Zarrini ldquoSynthe-sis in vitro antimicrobial and antioxidant activities of chalconeand flavone derivatives holding allylic substitutionsrdquoMedicinalChemistry Research vol 20 no 8 pp 1318ndash1324 2011

[12] K Parikh and D Joshi ldquoAntibacterial and antifungal screeningof newly synthesized benzimidazole-clubbed chalcone deriva-tivesrdquo Medicinal Chemistry Research vol 22 no 8 pp 3688ndash3697 2013

[13] J C Aponte M Verastegui E Malaga et al ldquoSynthesis cyto-toxicity and anti-Trypanosoma cruzi activity of new chalconesrdquoJournal of Medicinal Chemistry vol 51 no 19 pp 6230ndash62342008

[14] A Shah A M Khan R Qureshi F L Ansari M F Nazar andS S Shah ldquoRedox behavior of anticancer chalcone on a glassycarbon electrode and evaluation of its interaction parameterswith DNArdquo International Journal of Molecular Sciences vol 9no 8 pp 1424ndash1434 2008

[15] J Quintin J Desrivot S Thoret P L Menez T Cresteil andG Lewin ldquoSynthesis and biological evaluation of a series oftangeretin-derived chalconesrdquo Bioorganic amp Medicinal Chem-istry Letters vol 19 no 1 pp 167ndash169 2009

[16] S N Mokale P N Dube S A Bhavale et al ldquoSynthesis in-vitro screening and docking analysis of novel pyrrolidine andpiperidine-substituted ethoxy chalcone as anticancer agentsrdquoMedicinal Chemistry Research vol 24 no 5 pp 1842ndash18562015

[17] M Maggiolini G Statti A Vivacqua et al ldquoEstrogenic andantiproliferative activities of isoliquiritigenin in MCF7 breastcancer cellsrdquoThe Journal of Steroid Biochemistry and MolecularBiology vol 82 no 4-5 pp 315ndash322 2002

[18] T Sakai R N Eskander Y Guo et al ldquoFlavokawain B a kavachalcone induces apoptosis in synovial sarcoma cell linesrdquoJournal of Orthopaedic Research vol 30 no 7 pp 1045ndash10502012

[19] S K Kumar E Hager C Pettit H Gurulingappa N EDavidson and S R Khan ldquoDesign synthesis and evaluationof novel boronic-chalcone derivatives as antitumor agentsrdquoJournal of Medicinal Chemistry vol 46 no 14 pp 2813ndash28152003

[20] B Srinivasan T E Johnson R Lad and C Xing ldquoStructuremdashactivity relationship studies of chalcone leading to 3-hydroxy-4310158404101584051015840-tetramethoxychalcone and its analogues as potentnuclear factor 120581B inhibitors and their anticancer activitiesrdquoJournal of Medicinal Chemistry vol 52 no 22 pp 7228ndash72352009

[21] D Kumar N M Kumar K Akamatsu E Kusaka H Haradaand T Ito ldquoSynthesis and biological evaluation of indolyl chal-cones as antitumor agentsrdquo Bioorganic amp Medicinal ChemistryLetters vol 20 no 13 pp 3916ndash3919 2010

[22] S-H Kim E Lee K H Baek et al ldquoChalcones inhibitors fortopoisomerase i and cathepsin B and L as potential anti-canceragentsrdquo Bioorganic and Medicinal Chemistry Letters vol 23 no11 pp 3320ndash3324 2013

[23] H-J Zhang Y Qian D-D Zhu X-G Yang and H-L ZhuldquoSynthesis molecular modeling and biological evaluation of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

6 Journal of Chemistry

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

PC-3

cell

viab

ility

()

120

100

80

60

40

20

0

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

Con

trol

1120583

M

5120583

M

25120583

M

50120583

M

100120583

M

lowast

lowast

lowastlowast

lowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast lowastlowastlowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowast

lowastlowastlowastlowast

Compound D1 Compound 3a Compound 3b

Compound 3c Compound 3d Compound 3e

Compound 3f Compound 3g Compound 3h

Compound 3i Compound 3j

Figure 2 The relative cell viability () of PC-3 cells following the exposure of various concentrations of all the compounds (D1 and 3andashj)and untreated control cell for 24 h (lowast119901 lt 005 lowastlowast119901 lt 0001)

Journal of Chemistry 7

the chalcone compounds containing benzofuran ring In thisstudy we have firstly synthesized the chalcone compoundscontaining benzofuran ring And also we have firstly studiedon the anticancer properties of these compounds We havestudied only MCF-7 and PC-3 cells These results suggestedthat benzofuran substituted chalcones could be used as leadcompounds to develop novel potent anticancer agents

4 Conclusions

Synthetic benzofuran chalcone compounds were evaluatedin vitro for their anticancer activity by MTT assay Thebenzofuran substituted chalcone derivatives showed highantitumor activity against MCF-7 and PC-3 cell lines (119901 lt0001) These results displayed that chalcone derivativesbearing benzofuran ring may be useful in the future foranticancer drug development

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

The authors thank Fırat University for financial support ofthis work

References

[1] Y-L Chen S-Z Lin J-Y Chang et al ldquoIn vitro and in vivostudies of a novel potential anticancer agent of isochaihulactoneon human lung cancer A549 cellsrdquo Biochemical Pharmacologyvol 72 no 3 pp 308ndash319 2006

[2] R Abonia D Insuasty J Castillo et al ldquoSynthesis of novelquinoline-2-one based chalcones of potential anti-tumor activ-ityrdquo European Journal ofMedicinal Chemistry vol 57 pp 29ndash402012

[3] B-Z Ahn and D-E Sok ldquoMichael acceptors as a tool foranticancer drug designrdquo Current Pharmaceutical Design vol 2no 3 pp 247ndash262 1996

[4] Z Nowakowska ldquoA review of anti-infective and anti-infla-mmatory chalconesrdquo European Journal of Medicinal Chemistryvol 42 no 2 pp 125ndash137 2007

[5] X-W Zhang D-H Zhao Y-C Quan L-P Sun X-M Yinand L-P Guan ldquoSynthesis and evaluation of antiinflammatoryactivity of substituted chalcone derivativesrdquo Medicinal Chem-istry Research vol 19 no 4 pp 403ndash412 2010

[6] H Iqbal V Prabhakar A Sangith B Chandrika and RBalasubramanian ldquoSynthesis anti-inflammatory and antioxi-dant activity of ring-a-monosubstituted chalcone derivativesrdquoMedicinal Chemistry Research vol 23 no 10 pp 4383ndash43942014

[7] M Wan L Xu L Hua et al ldquoSynthesis and evaluation of novelisoxazolyl chalcones as potential anticancer agentsrdquo BioorganicChemistry vol 54 pp 38ndash43 2014

[8] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoAntimalarial activity and synthesis of new trisubstitutedpyrimidinesrdquo Bioorganic and Medicinal Chemistry Letters vol15 no 12 pp 3130ndash3132 2005

[9] M L Go X Wu and X L Liu ldquoChalcones an update oncytotoxic and chemoprotective propertiesrdquo Current MedicinalChemistry vol 12 no 4 pp 483ndash499 2005

[10] P M Sivakumar S Ganesan P Veluchamy and M DobleldquoNovel chalcones and 135-triphenyl-2-pyrazoline derivativesas antibacterial agentsrdquo Chemical Biology amp Drug Design vol76 no 5 pp 407ndash411 2010

[11] H Adibi J S Mojarrad H Asgharloo and G Zarrini ldquoSynthe-sis in vitro antimicrobial and antioxidant activities of chalconeand flavone derivatives holding allylic substitutionsrdquoMedicinalChemistry Research vol 20 no 8 pp 1318ndash1324 2011

[12] K Parikh and D Joshi ldquoAntibacterial and antifungal screeningof newly synthesized benzimidazole-clubbed chalcone deriva-tivesrdquo Medicinal Chemistry Research vol 22 no 8 pp 3688ndash3697 2013

[13] J C Aponte M Verastegui E Malaga et al ldquoSynthesis cyto-toxicity and anti-Trypanosoma cruzi activity of new chalconesrdquoJournal of Medicinal Chemistry vol 51 no 19 pp 6230ndash62342008

[14] A Shah A M Khan R Qureshi F L Ansari M F Nazar andS S Shah ldquoRedox behavior of anticancer chalcone on a glassycarbon electrode and evaluation of its interaction parameterswith DNArdquo International Journal of Molecular Sciences vol 9no 8 pp 1424ndash1434 2008

[15] J Quintin J Desrivot S Thoret P L Menez T Cresteil andG Lewin ldquoSynthesis and biological evaluation of a series oftangeretin-derived chalconesrdquo Bioorganic amp Medicinal Chem-istry Letters vol 19 no 1 pp 167ndash169 2009

[16] S N Mokale P N Dube S A Bhavale et al ldquoSynthesis in-vitro screening and docking analysis of novel pyrrolidine andpiperidine-substituted ethoxy chalcone as anticancer agentsrdquoMedicinal Chemistry Research vol 24 no 5 pp 1842ndash18562015

[17] M Maggiolini G Statti A Vivacqua et al ldquoEstrogenic andantiproliferative activities of isoliquiritigenin in MCF7 breastcancer cellsrdquoThe Journal of Steroid Biochemistry and MolecularBiology vol 82 no 4-5 pp 315ndash322 2002

[18] T Sakai R N Eskander Y Guo et al ldquoFlavokawain B a kavachalcone induces apoptosis in synovial sarcoma cell linesrdquoJournal of Orthopaedic Research vol 30 no 7 pp 1045ndash10502012

[19] S K Kumar E Hager C Pettit H Gurulingappa N EDavidson and S R Khan ldquoDesign synthesis and evaluationof novel boronic-chalcone derivatives as antitumor agentsrdquoJournal of Medicinal Chemistry vol 46 no 14 pp 2813ndash28152003

[20] B Srinivasan T E Johnson R Lad and C Xing ldquoStructuremdashactivity relationship studies of chalcone leading to 3-hydroxy-4310158404101584051015840-tetramethoxychalcone and its analogues as potentnuclear factor 120581B inhibitors and their anticancer activitiesrdquoJournal of Medicinal Chemistry vol 52 no 22 pp 7228ndash72352009

[21] D Kumar N M Kumar K Akamatsu E Kusaka H Haradaand T Ito ldquoSynthesis and biological evaluation of indolyl chal-cones as antitumor agentsrdquo Bioorganic amp Medicinal ChemistryLetters vol 20 no 13 pp 3916ndash3919 2010

[22] S-H Kim E Lee K H Baek et al ldquoChalcones inhibitors fortopoisomerase i and cathepsin B and L as potential anti-canceragentsrdquo Bioorganic and Medicinal Chemistry Letters vol 23 no11 pp 3320ndash3324 2013

[23] H-J Zhang Y Qian D-D Zhu X-G Yang and H-L ZhuldquoSynthesis molecular modeling and biological evaluation of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 7

the chalcone compounds containing benzofuran ring In thisstudy we have firstly synthesized the chalcone compoundscontaining benzofuran ring And also we have firstly studiedon the anticancer properties of these compounds We havestudied only MCF-7 and PC-3 cells These results suggestedthat benzofuran substituted chalcones could be used as leadcompounds to develop novel potent anticancer agents

4 Conclusions

Synthetic benzofuran chalcone compounds were evaluatedin vitro for their anticancer activity by MTT assay Thebenzofuran substituted chalcone derivatives showed highantitumor activity against MCF-7 and PC-3 cell lines (119901 lt0001) These results displayed that chalcone derivativesbearing benzofuran ring may be useful in the future foranticancer drug development

Competing Interests

The authors declare that they have no competing interests

Acknowledgments

The authors thank Fırat University for financial support ofthis work

References

[1] Y-L Chen S-Z Lin J-Y Chang et al ldquoIn vitro and in vivostudies of a novel potential anticancer agent of isochaihulactoneon human lung cancer A549 cellsrdquo Biochemical Pharmacologyvol 72 no 3 pp 308ndash319 2006

[2] R Abonia D Insuasty J Castillo et al ldquoSynthesis of novelquinoline-2-one based chalcones of potential anti-tumor activ-ityrdquo European Journal ofMedicinal Chemistry vol 57 pp 29ndash402012

[3] B-Z Ahn and D-E Sok ldquoMichael acceptors as a tool foranticancer drug designrdquo Current Pharmaceutical Design vol 2no 3 pp 247ndash262 1996

[4] Z Nowakowska ldquoA review of anti-infective and anti-infla-mmatory chalconesrdquo European Journal of Medicinal Chemistryvol 42 no 2 pp 125ndash137 2007

[5] X-W Zhang D-H Zhao Y-C Quan L-P Sun X-M Yinand L-P Guan ldquoSynthesis and evaluation of antiinflammatoryactivity of substituted chalcone derivativesrdquo Medicinal Chem-istry Research vol 19 no 4 pp 403ndash412 2010

[6] H Iqbal V Prabhakar A Sangith B Chandrika and RBalasubramanian ldquoSynthesis anti-inflammatory and antioxi-dant activity of ring-a-monosubstituted chalcone derivativesrdquoMedicinal Chemistry Research vol 23 no 10 pp 4383ndash43942014

[7] M Wan L Xu L Hua et al ldquoSynthesis and evaluation of novelisoxazolyl chalcones as potential anticancer agentsrdquo BioorganicChemistry vol 54 pp 38ndash43 2014

[8] A Agarwal K Srivastava S K Puri and P M S ChauhanldquoAntimalarial activity and synthesis of new trisubstitutedpyrimidinesrdquo Bioorganic and Medicinal Chemistry Letters vol15 no 12 pp 3130ndash3132 2005

[9] M L Go X Wu and X L Liu ldquoChalcones an update oncytotoxic and chemoprotective propertiesrdquo Current MedicinalChemistry vol 12 no 4 pp 483ndash499 2005

[10] P M Sivakumar S Ganesan P Veluchamy and M DobleldquoNovel chalcones and 135-triphenyl-2-pyrazoline derivativesas antibacterial agentsrdquo Chemical Biology amp Drug Design vol76 no 5 pp 407ndash411 2010

[11] H Adibi J S Mojarrad H Asgharloo and G Zarrini ldquoSynthe-sis in vitro antimicrobial and antioxidant activities of chalconeand flavone derivatives holding allylic substitutionsrdquoMedicinalChemistry Research vol 20 no 8 pp 1318ndash1324 2011

[12] K Parikh and D Joshi ldquoAntibacterial and antifungal screeningof newly synthesized benzimidazole-clubbed chalcone deriva-tivesrdquo Medicinal Chemistry Research vol 22 no 8 pp 3688ndash3697 2013

[13] J C Aponte M Verastegui E Malaga et al ldquoSynthesis cyto-toxicity and anti-Trypanosoma cruzi activity of new chalconesrdquoJournal of Medicinal Chemistry vol 51 no 19 pp 6230ndash62342008

[14] A Shah A M Khan R Qureshi F L Ansari M F Nazar andS S Shah ldquoRedox behavior of anticancer chalcone on a glassycarbon electrode and evaluation of its interaction parameterswith DNArdquo International Journal of Molecular Sciences vol 9no 8 pp 1424ndash1434 2008

[15] J Quintin J Desrivot S Thoret P L Menez T Cresteil andG Lewin ldquoSynthesis and biological evaluation of a series oftangeretin-derived chalconesrdquo Bioorganic amp Medicinal Chem-istry Letters vol 19 no 1 pp 167ndash169 2009

[16] S N Mokale P N Dube S A Bhavale et al ldquoSynthesis in-vitro screening and docking analysis of novel pyrrolidine andpiperidine-substituted ethoxy chalcone as anticancer agentsrdquoMedicinal Chemistry Research vol 24 no 5 pp 1842ndash18562015

[17] M Maggiolini G Statti A Vivacqua et al ldquoEstrogenic andantiproliferative activities of isoliquiritigenin in MCF7 breastcancer cellsrdquoThe Journal of Steroid Biochemistry and MolecularBiology vol 82 no 4-5 pp 315ndash322 2002

[18] T Sakai R N Eskander Y Guo et al ldquoFlavokawain B a kavachalcone induces apoptosis in synovial sarcoma cell linesrdquoJournal of Orthopaedic Research vol 30 no 7 pp 1045ndash10502012

[19] S K Kumar E Hager C Pettit H Gurulingappa N EDavidson and S R Khan ldquoDesign synthesis and evaluationof novel boronic-chalcone derivatives as antitumor agentsrdquoJournal of Medicinal Chemistry vol 46 no 14 pp 2813ndash28152003

[20] B Srinivasan T E Johnson R Lad and C Xing ldquoStructuremdashactivity relationship studies of chalcone leading to 3-hydroxy-4310158404101584051015840-tetramethoxychalcone and its analogues as potentnuclear factor 120581B inhibitors and their anticancer activitiesrdquoJournal of Medicinal Chemistry vol 52 no 22 pp 7228ndash72352009

[21] D Kumar N M Kumar K Akamatsu E Kusaka H Haradaand T Ito ldquoSynthesis and biological evaluation of indolyl chal-cones as antitumor agentsrdquo Bioorganic amp Medicinal ChemistryLetters vol 20 no 13 pp 3916ndash3919 2010

[22] S-H Kim E Lee K H Baek et al ldquoChalcones inhibitors fortopoisomerase i and cathepsin B and L as potential anti-canceragentsrdquo Bioorganic and Medicinal Chemistry Letters vol 23 no11 pp 3320ndash3324 2013

[23] H-J Zhang Y Qian D-D Zhu X-G Yang and H-L ZhuldquoSynthesis molecular modeling and biological evaluation of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

8 Journal of Chemistry

chalcone thiosemicarbazide derivatives as novel anticanceragentsrdquo European Journal of Medicinal Chemistry vol 46 no9 pp 4702ndash4708 2011

[24] A Kamal J S Reddy M J Ramaiah et al ldquoDesign synthe-sis and biological evaluation of imidazopyridinepyrimidine-chalcone derivatives as potential anticancer agentsrdquo MedicinalChemical Communications vol 1 no 5 pp 355ndash360 2010

[25] A Sharma B ChakravartiM PGupt J A Siddiqui R Konwarand R P Tripathi ldquoSynthesis and anti breast cancer activity ofbiphenyl based chalconesrdquoBioorganic andMedicinal Chemistryvol 18 no 13 pp 4711ndash4720 2010

[26] K JuvaleV F S Pape andMWiese ldquoInvestigation of chalconesand benzochalcones as inhibitors of breast cancer resistanceproteinrdquo Bioorganic and Medicinal Chemistry vol 20 no 1 pp346ndash355 2012

[27] V Ugale H Patel B Patel and S Bari ldquoBenzofurano-isatinssearch for antimicrobial agentsrdquo Arabian Journal of Chemistry2012

[28] C-L Kao and J-W Chern ldquoA convenient synthesis of naturallyoccurring benzofuran ailanthoidolrdquoTetrahedron Letters vol 42no 6 pp 1111ndash1113 2001

[29] R Basawaraj B Yadav and S S Sangapure ldquoSynthesis ofsome 1H-pyrazolines bearing benzofuran as biologically activeagentsrdquo Indian Journal of Heterocyclic Chemistry vol 11 no 1pp 31ndash34 2001

[30] S M Rida S A M El-Hawash H T Y Fahmy A A Hazzaaand M M M El-Meligy ldquoSynthesis of novel benzofuran andrelated benzimidazole derivatives for evaluation of in vitroanti-HIV-1 anticancer and antimicrobial activitiesrdquo Archives ofPharmacal Research vol 29 no 10 pp 826ndash833 2006

[31] R K Ujjinamatada R S Appala and Y S AgasimundinldquoSynthesis and antimicrobial activity of new benzofuranyl-13-benzoxazines and 13-benzoxazin-2-onesrdquo Journal of Hetero-cyclic Chemistry vol 43 no 2 pp 437ndash441 2006

[32] R Romagnoli P G Baraldi T Sarkar et al ldquoSynthesis and bio-logical evaluation of 2-aroyl-4-phenyl-5-hydroxybenzofuransas a new class of antitubulin agentsrdquo Medicinal Chemistry vol4 no 6 pp 558ndash564 2008

[33] Y C Mayur G J Peters V V S Rajendra Prasad C Lemosand N K Sathish ldquoDesign of new drug molecules to be used inreversing multidrug resistance in cancer cellsrdquo Current CancerDrug Targets vol 9 no 3 pp 298ndash306 2009

[34] V R Solomon C Hu and H Lee ldquoHybrid pharmacophoredesign and synthesis of isatin-benzothiazole analogs for theiranti-breast cancer activityrdquo Bioorganic and Medicinal Chem-istry vol 17 no 21 pp 7585ndash7592 2009

[35] D Coskun andM Ahmedzade ldquo3-(Substituted aryl)-1-(benzo-furan-2-yl)-2-propenones part 1 synthesis and characteriza-tion of some novel chalconesrdquo Synthetic Communications vol38 no 21 pp 3613ndash3622 2008

[36] H Kucukbay AMumcu S Tekin and S Sandal ldquoSynthesis andevaluation of novel NNrsquo-disubstituted benzimidazolium bro-mides salts as antitumor agentsrdquo Turkish Journal of Chemistryvol 40 pp 393ndash401 2016

[37] N Kolocouris G B Foscolos A Kolocouris et al ldquoSynthesisand antiviral activity evaluation of some aminoadamantanederivativesrdquo Journal of Medicinal Chemistry vol 37 no 18 pp2896ndash2902 1994

[38] A O Gorgulu K Koran F Ozen S Tekin and S SandalldquoSynthesis structural characterization and anti-carcinogenicactivity of new cyclotriphosphazenes containing dioxybiphenyl

and chalcone groupsrdquo Journal of Molecular Structure vol 1087pp 1ndash10 2015

[39] R A Kabli A A Khalaf M T Zimaity A M Khalil A MKaddah and H A Al-Rifaie ldquoSynthesıs of a new serıes offuryl and thıenyl substıtuted pyrazolınes startıng wıth furyl andthıenyl chalconesrdquo Journal of the Indian Chemical Society vol68 pp 47ndash51 1991

[40] B S Holla P M Akberali and M K Shivananda ldquoStudieson arylfuran derivatives part X Synthesis and antibacterialproperties of arylfuryl-Δ2-pyrazolinesrdquo Farmaco vol 55 no 4pp 256ndash263 2000

[41] M Cabrera M Simoens G Falchi et al ldquoSynthetic chal-cones flavanones and flavones as antitumoral agents biologicalevaluation and structure-activity relationshipsrdquo Bioorganic andMedicinal Chemistry vol 15 no 10 pp 3356ndash3367 2007

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of