“SYNTHESES, CHARACTERIZATION AND ANTIMICROBIAL SCREENING OF SOME NEW POLYSUBSTITUTED

OXADIAZOLES AND THIOPHENES”

SYNOPSIS FORM.PHARM. DISSERTATION

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCESKARNATAKA

BYMR AKASH DAS

I M.PHARMDEPARTMENT OF PHARMACEUTICAL CHEMISTRY

PES COLLEGE OF PHARMACYBANGALORE-560 050

(2012-2014)

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. Name of the candidate and address

MR. AKASH DASΙ. M. PHARM(PHARMACEUTICAL CHEMISTRY)PES COLLEGE OF PHARMACYHANUMANTHANAGARBANGALORE-560 050

PERMANENT ADDRESS:C/O MR CHAMPAK DASPURE SITALPUR COLLIERYPOST-UKHRADISTRICT-BURDWANPIN-713322WEST BENGAL

2. Name of the institution PES COLLEGE OF PHARMACYHANUMANTHANAGARB.S.K.1st STAGEBANGALORE:-560 050

3. Course of the study MASTER OF PHARMACY (PHARMACEUTICAL CHEMISTRY)

4. Date of Admission 22nd JUNE 2012

5. Title of the topic:

“SYNTHESES,CHARACTERIZATION AND ANTIMICROBIAL SCREENING OF SOME NEW POLYSUBSTITUTED OXADIAZOLES AND THIOPHENES ”

6. BRIEF RESUME OF THE INTENDED WORK

6.1 Need for the study:

A large number of oxadiazoles and thiophenes have been prepared and many of these

compounds have shown a wide spectrum of antimicrobial activity. The observation that, some

oxadiazoles/thiophenes with different substituents at different location on the heterocyclic ring

resulted in fungicidal and antibacterial activity of various potencies. Since their discovery during

the 20th century, antimicrobial agents (antibiotics and related antimicrobial drugs) have

substantially reduced the threat posed by infectious diseases. The use of these "wonder drugs",

combined with improvements in sanitation, housing, and nutrition, and the advent of widespread

immunization programme, and the development of numbers of antimicrobial agents for treatment

of microbial infections has led to a dramatic drop in deaths from diseases that were previously

widespread, untreatable, and frequently fatal. These gains are now seriously jeopardized by

another recent development: the emergence and spread of microbes that are resistant to cheap and

effective first choice, or "first-line" drugs. Worldwide emergence of multi-resistant microbial

strains is a growing concern which requires a multi-pronged research strategy.

6.2 Review of the literature :

References pertaining to Oxadiazoles:

1. Vishal Modi et al., reported the synthesis and evaluation of some oxadiazoles like 4-(decyloxy)-N-(4-(5-(tetradecylthio)-1,3,4-oxadiazol-2-yl)phenyl)benzamide having good anti-microbial activity. [2012]

(1)

2. Manav Malhotra et al., reported the synthesis and anti-microbial activity of (Z)-N-(1-(2-(3-((dimethylamino)methyl)-2-methoxyphenyl)-5-(pyridine-4-yl)-1,3,4-oxadiazol-3(2H)-yl)ethylidene)-benzenamine derivatives. [2012]

R= -H, -F, -Cl, -Br, -NO2, -OCH3

(2)

3. Ali Hussain Raheemah et al., reported the synthesis and anti-microbial action of 1-[3-(4-butoxyphenyl)-1,2,4-oxadiazole-5-yl]-4-[5-(n-substituted phenyl)-1,3,4-oxadiazole-2-yl]-benzene derivatives against Gram-positive bacteria. [2012]

X= -H, -CH3, -Cl, -NO2, -OCH3

(3)

4. Yao Li et al., synthesized and evaluated the anti-microbial activity of nitroimidazole derivatives containing 1,3,4-oxadiazole scaffold.[2012]

4(a) 4(b)

R1 & R2 = -CH3, -F, -Cl, -Br, -NO2, -OCH3

5. Palak K. Parikh et al., synthesized and studied the anti-bacterial activity of 2-[5-(substituted

sulfanyl)-1,3,4-oxadiazol-2-yl]phenol derivatives. [2011]

R= , , ,

(5)

6. P.Panneerselvam et al., synthesized compounds like 4-((5-(2-Fluorophenyl)-1,3,4-oxadiazol-2-yl)methoxy)phenylacetamide as good antimicrobial agent. [2011]

(6)

7. Synthesis and anti-microbial activity of 1-(5-(3,5-dichlorobenzo[b]thiophen-2-yl)-2-(4-methoxyphenyl)-1,3,4-oxadiazol-3(2H)-yl)ethanone was reported by KM Thaker et al. [2011]

(7)

8. Anil N. Mayekar et al., reported the synthesis and anti-microbial action of substituted 1,3,4-oxadiazole derivatives bearing 6-bromonaphthalene moiety.[2010]

(8) R= Aryl Grp.

9. B. Chandrakantha et al., synthesized and evaluated the antibacterial and anti fungal action of

novel 2-(2-fluoro-4-methoxyphenyl)-5-substituted-1,3,4-oxadiazoles like 2-(3-bromo-2-methylphenyl)-5-(2-fluoro-4-methoxyphenyl)-1,3,4-oxadiazole.[2010]

(9)

10. Zuhair Muhi-eldeen et al., reported the synthesis and anti-bacterial action of 5-phenyl-1,3,4-oxadiazole-2-carbamates such as O-ethyl S-5-phenyl-1,3,4-oxadiazol-2-yl carbonothioate . [2008]

(10)

References pertaining to Thiophenes:

11. Aisha S. M. Hossan et al., synthesized and reported the evaluation of pyrimidinone and oxazinone derivatives fused with thiophene ring like 7-(2-Chloro-6-ethoxypyridin-4-yl)-9-(4-chlorophenyl)-2-methyl-4H-pyrido[3',2':4,5]thieno[3,2-d]-[1,3]oxazin-4-one.[2012]

(11)

12. B.V Guruprasad et al., reported the synthesis and antimicrobial activity of thiophene-2-carboxamides like (Z)-3-chloro-N'-((2-hydroxyquinolin-3-yl)methylene)benzo[b]thiophene-2-carbohydrazide.[2012]

(12)

13. Nabila Abdelshafy Khedar et al., synthesized bis-[1,3,4]thiadiazoles having thieno[2,3b]thiophene moiety with activity against Gram-positive bacteria.[2012]

R1= Ph, EtOCO, MeCOR2= Ph, 4-MePh, 4-ClPh

(13)

14. Yerra Rajeshwar et al., reported the antimicrobial activity of Thieno[2,3-d] pyrimidine like (E)-N-(4-chlorobenzylidene)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine.[2012]

(14)

15. Mohammad Asif Iqbal et al., reported the antimicrobial screening of some novel substituted Thiophenes like (E)-2-(4-methoxybenzylideneamino)-N-(furan-2-ylmethyl)-4,5-dimethylthiophene-3-carboxamide.[2012]

(15)

16. Hala M. Aly et al., reported the design and synthesis of some new thiophene, thienopyrimidine derivatives of antipyrine as potential antimicrobial agents.[2011]

(16)

17. Samir Bondock et al., reported synthesis of thiophene derivatives with benzothiazole moiety like 2-amino-N-(benzothiazol-2-yl)-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide.[2010]

(17)

18. M.A. Gouda et al., reported the synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4,5,6,7-tetrahydrobenzothiophene moiety.[2010]

(18)

19. A.M. Khalil et al., reported the synthesis and antibacterial activity of some new thiophene derivatives.[2009]

R=COCH3,COOC2H5, CN (19)

20. M Raghuprasad et al ., reported the synthesis and antimicribial activity of some thiadiazolo thienopyrimidines.[2007]

R=OCH3

(20)

In the view of the above observations it was thought of interest to synthesize and screen some new Oxadiazoles and Thiophenes for anti-microbial activity.

6.3 SCHEMES

6.3.1 SCHEME I

Synthesis of new polysubstituted oxadiazoles

6.3.2 SCHEME II

Synthesis of new polysubstituted thiophenes

6.4 OBJECTIVES OF THE STUDY:

1. To achieve the syntheses of some new substituted Oxadiazoles and Thiophenes following standard procedures.

2. The purity and progress of the reactions will be monitored by TLC.

3. The purification of the compounds will be carried out by recrystallization using suitable solvents.

4. To characterize the structures of newly synthesized compounds by UV, IR, NMR, CHN analysis and MASS spectra.

5. To evaluate the anti-microbial activity of new compounds by standard protocols and to study the structure-activity relationships and to optimize the structure.

6. To publish the research work in peer reviewed journals.

7.1 MATERIALS AND METHODS:

Chemicals and other reagents will be purchased from standard companies. The progress of the reactions will be monitored by micro thin layer chromatography. The standard protocols will be followed for purification of the products. Structures of the synthesized molecules will be confirmed by the analytical and spectral data. The biological screening results will be used to study structure-activity relationships.

7.2 Sources of data

IISC LIBRARY, BANGALOREPESCP LIBRARY, BANGALORERGUHS DIGITAL LIBRARY (Helinet)CENTRAL COLLEGE LIBRARY, BANGALORE

7.3 Method of collection of data

Chemical Abstracts, Journals like Indian Journal of Chemistry, Journal of Medicinal Chemistry, Indian Journal of Heterocyclic Chemistry, Journal of American Chemical Society, Indian Journal of Pharmaceutical Sciences, International journal of Bioscience, Asian Journal of Medicinal Chemistry, Journal of Organic chemistry, European Journal of Medicinal Chemistry, Tetrahedron, Bioorganic & Medicinal Chemistry and Helinet.

7.4 Pharmacological Screening:

The evaluation of antimicrobial activity of new polysubstituted oxadiazoles and thiophenes is going to be carried out by using cup plate method.

7.5 Does the study require any investigation or interventions to be conducted on patients or other humans or animals?

-NO-

7.6 Has ethical clearance been obtained from your institution in case of 7.5?

-NOT APPLICABLE-

LIST OF REFERENCES:

1. Modi V, Modi P. Oxadiazole: Synthesis, characterizationand biological activities. Journal of Saudi Chemical Society. 2012;16: 327–322. Malhotra M, Sanduja M, Samad A, Deep A. New oxadiazole derivatives of isonicotinohydrazide in the search for antimicrobial agents: Synthesis and in vitro evaluation. J Serb Chem Soc. (2012;77( (1)):9-16.3. Raheemah AH, Al-Daraji. Synthesis and antibacterial activity of bis-oxadiazole derivatives. Iraqi National Journal of Chemistry. 2012;46: 229- 39.4. Li Y, Luo Y, Hu Y, Zhu D-D, Zhang S, Liu Z-J, et al. Design, synthesis and antimicrobial activities of nitroimidazole derivatives containing 1,3,4-oxadiazole scaffold as FabH inhibitors. Bioorganic & Medicinal Chemistry. 2012;20:4316-22.5. Parikh PK, Marvaniya HM, Sen DJ. Synthesis And Biological Evaluation of 1,3,4-Oxadiazole Derivatives as Potential Antibacterial and Antifungal Agents.. International Journal of Drug Development & Research. 2011;3(2):248-55.6. Panneerselvam P, Gansha GG. Synthesis and Antimicrobial Screening of Some Novel 2, 5-Disubstituted 1, 3, 4-oxadiazole Derivatives. E-Journal of Chemistry. 2011;8:149-54.7. Thaker KM, Ghetiya RM, Tala SD, Dodiya BL, Joshi KA, Dubal KL, et al. Synthesis of oxadiazoles and pyrazolones as a antimycobacterial and antimicrobial agents. Indian Journal of Chemistry 2011;50B:738-44.8. Mayekar AN, Yathirajan HS, Narayana B, Sarojini BK, Kumari NS. Synthesis and Antimicrobial Studies on New Substituted 1,3,4-Oxadiazole Derivatives Bearing 6-Bromonapthalene Moiety. International journal of chemistry. 2010;2(1):38-54.9. Chandrakantha B, Shetty P, Nambiyar V, Isloor N, Isloor AM. Synthesis, characterization and biological activity of some new 1,3,4-oxadiazole bearing 2-flouro-4-methoxy phenyl moiety. European Journal of Medicinal Chemistry. 2010;45:1206-10.10. Muhi-eldeen Z, Juma'a G, Al – kaissi E, Nouri L. Antimicrobial Activity of Some New Oxadiazole Derivatives. Jordan journal of chemistry. 2008;3(3):233-43.11. Hossan ASM, Abu-Melha HMA, Al-Omar MA, Amr AE-GE. Synthesis and Antimicrobial Activity of Some New Pyrimidinone and Oxazinone Derivatives Fused with Thiophene Rings Using 2-Chloro-6-ethoxy-4-acetylpyridine as Starting Material. Molecules 2012;17:13642-55.12. Guruprasad BV, Mruthyunayaswamy BHM. Synthesis and antimicrobial activity of some new 3-chloro-6-substituted -N-(substituted 2H-[1,3]oxazino[6,5-b]quinolin-3-(4H,5aH,9aH)-yl)benzo[b]thiopene-2-carboxamides. Indian Journal of Chemistry. 2012;51B:514-20.13. Kheder NA, Mabkhot YN. Synthesis and Antimicrobial Studies of Some Novel Bis-[1,3,4]thiadiazole and Bis-thiazole Pendant to Thieno[2,3-b]thiophene Moiety. International Journal of Molercular Sciences. 2012;13(3):3661–70.14. Rajeshwar Y, Naresh K, Jayaveera KN. Synthesis and Antimicrobial Studies of Some Novel Thieno[2,3-d]pyrimidine derivatives. International Journal of PharmTech Research. 2012;4(2):648-54.15. Iqbal MA, Satyendra D, Apurba T, Patel M, Monika K, Girish K, et al. Synthesis and Antimicrobial screening of some Novel Substituted Thiophenes. Hygeia Journal for Drugs & Medicines. 2012;4(1):112-8.

16. Aly H, Saleh N, Elhady H. The design and synthesis of some new thiophene, thienopyrimidine and thienothiadiazine derivatives of antipyrine as potential antimicrobial agents. Euro J Med Chem. 2011;46:4566-72.17. Bondock S, Fadaly W, Metwally MA. Synthesis and antimicrobial activity of some new thiazole, thiophene and pyrazole derivatives containing benzothiazole moiety. European Journal of Medicinal Chemistry 2010;45:3692-701.18. Gouda MA, Berghot MA, Abd El-Ghani GE, Khalil AM. The synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4,5,6,7-tetrahydrobenzothiophene moiety. Euro J Med Chem. 2010;45:1338–45.19. Khalil AM, Berghot MA, Gouda MA. Synthesis and antibacterial activity of some new thiazole and thiophene derivatives. Euro J Med Chem. 2009;44:4434-40.20. Raghuprasad M, Mohan S, Das B, Srivastava S. Synthesis and antimicribial activity of some thiadiazolo thienopyrimidines. Asian J Chem. 2007;19(5):2813-7.

9 Signature of the candidate :

(AKASH DAS)

10. Remarks of the guide: FORWARDED WITH REQUEST FOR APPROVAL

11. Name and designation of: 11.1 GUIDE

11.2 SIGNATURE

Dr. J. SARAVANAN

Prof. and HODDepartment of Pharm Chemistry,

PES College of PharmacyBangalore- 560 050

11.3 CO-GUIDE

11.4 SIGNATURE

NOT APPLICABLE

11.5 HEAD OF THE DEPARTMENT

11.6 SIGNATURE

Dr. J. SaravananProf. and HOD

Department of Pharm Chemistry,PES College of Pharmacy

Bangalore- 560 050

12. 12.1 REMARKS OF THE PRINCIPAL:

12.2 SIGNATURE: Prof. Dr. S. Mohan Principal & Director, PES College of Pharmacy, Bangalore-560 050