Review Article Naturally Occurring Xanthones: Chemistry and ...Journal of Applied Chemistry ...O-Glycosides. MorethanxanthoneO-glycosidesare known. A few are from natural sources,

RetractionRetractedNaturallyOccurringXanthonesChemistryandBiology

Journal of Applied Chemistry

Received 3 February 2021 Accepted 3 February 2021 Published 15 March 2021

Copyright copy 2021 Journal of Applied Chemistry is is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in anymedium provided the original work isproperly cited

Journal of Applied Chemistry has retracted the article titledldquoNaturally Occurring Xanthones Chemistry and Biologyrdquo[1] e article was found to contain a substantial amount ofoverlapping material from previously published articlesincluding the following sources cited as [2ndash5]

(i) Kurt Hostettmann Hildebert Wagner ldquoXanthoneglycosidesrdquo Phytochemistry Volume 16 Issue 71977 Pages 821ndash829 ISSN 0031-9422 doi 101016S0031-9422(00)86673-X [2]

(ii) L MM Vieira A Kijjoa Naturally-occurringxanthones recent developments Current MedicinalChemistry Volume 12 Issue 21 2005 doi 102174092986705774370682 [3]

(iii) S R Jensen J Schripsema Chemotaxonomy andpharmacology of Gentianaceae In Lena StruweVictor A Albert (eds) Gentianaceae 573-632January 2001 doi 101017cbo9780511541865007[4]

(iv) Ozlem Demirkiran (2007) Xanthones in Hyper-icum synthesis and biological activities In KhanM T H (eds) Bioactive Heterocycles III Topics inHeterocyclic Chemistry vol 9 Springer BerlinHeidelberg Germany doi 1010077081_2007_079[5]

Additionally 507 words were reproduced from theauthorsʼ earlier review article [6] cited as reference 108 inthe article

e article is being retracted due to this overlap with theagreement of the editorial board e authors did not re-spond to these concerns

References

[1] S Negi V K Bisht P Singh M S M Rawat and G P JoshildquoNaturally occurring xanthones chemistry and biologyrdquoJournal of Applied Chemistry vol 2013 Article ID 6214599 pages 2013

[2] H Kurt and H Wagner ldquoXanthone glycosidesrdquo Phytochem-istry vol 16 no 7 pp 821ndash829 1977

[3] L M M Vieira and A Kijjoa ldquoNaturally-occurring xanthonesrecent developmentsrdquo Current Medicinal Chemistry vol 12no 21 2005

[4] S R Jensen and J Schripsema ldquoChemotaxonomy and phar-macology of Gentianaceaerdquo in Gentianaceae-Systematics andNatural History V A Albert Ed Cambridge University PressCambridge UK 2001

[5] O Demirkiran ldquoXanthones in Hypericum synthesis and bi-ological activitiesrdquo in Bioactive Heterocycles III Topics inHeterocyclic Chemistry M T H Khan Ed Springer BerlinHeidelberg Germany 2007

[6] J S Negi P Singh and B Rawat ldquoChemical constituents andbiological importance of Swertia a reviewrdquoCurrent Research inChemistry vol 3 pp 1ndash15 2011

HindawiJournal of Applied ChemistryVolume 2021 Article ID 8725409 1 pagehttpsdoiorg10115520218725409

Hindawi Publishing CorporationJournal of Applied ChemistryVolume 2013 Article ID 621459 9 pageshttpdxdoiorg1011552013621459

Review ArticleNaturally Occurring Xanthones Chemistry and Biology

J S Negi1 V K Bisht1 P Singh2 M S M Rawat2 and G P Joshi2

1 Herbal Analytical Laboratory Herbal Research and Development Institute Mandal Gopeshwar Uttarakhand 246401 India2Department of Chemistry HNB Garhwal University Srinagar Garhwal Uttarakhand 246174 India

Correspondence should be addressed to J S Negi negijsyahoocom

Received 4 April 2013 Accepted 24 September 2013

Academic Editor Ming-Jer Lee

Copyright copy 2013 J S Negi et alThis is an open access article distributed under the Creative Commons Attribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Xanthones are one of the biggest classes of compounds in natural product chemistry A number of xanthones have been isolatedfrom natural sources of higher plants fungi ferns and lichens They have gradually risen to great importance because of theirmedicinal properties This review focuses on the types isolation characterization biological applications and biosynthesis ofnaturally occurring xanthones isolated so far Different physicochemical and instrumental methods such as liquid-solid andliquid-liquid extraction TLC flash chromatography column chromatography IR 1H NMR and 13C NMR spectroscopy GLCHPLC GC and LCMS have been widely used for isolation and structural elucidation of xanthones Hepatoprotective anti-carcinogenic antileprosy antimalarial antioxidant anticholinergic mutagenicity radioprotective immunomodulatory antiboneresorption antiparasitic neuraminidase inhibitory anticomplement antibacterial antifungal algicidal anti-HIV cardioprotectiveantitumoral antidiabetes antihyperlipidemic antiatherogenic anti-inflammatory antiulcer antidiabetic hypolipidemic analgesicantiasthmatic antihistaminic antiamoebic diuretic antidiarrheal larvicidal and ovicidal activities have been reported for naturaloccurring xanthones To a certain extent this review provides necessary foundation for further research and development of newmedicines

1 Introduction

Xanthones are secondary metabolites commonly occurringin higher plant families fungi and lichen [1] Their phar-macological properties have raised great interest Structuresof xanthones are related to that of flavonoids and theirchromatographic behaviours are also similar Flavonoids arefrequently encountered in nature whereas xanthones arefound in limited number of families Xanthones always occurin the families Gentianaceae Guttiferae Moraceae Clusi-aceae and Polygalaceae Xanthones are sometimes foundas the parent polyhydroxylated compounds but most aremono- or polymethyl ethers or are found as glycosides [2]Unlike iridoids xanthones are apparently not present in allplant species investigated in the family Gentianaceae Thisis documented by the systematic work of Hostettmann etal [3] Natural occurrence of 12 xanthones in higher plantsand 4 in fungi has been reviewed by Roberts in 1961 and byDean in 1963 [4 5] Gottlieb [6] mentioned the isolation of60 xanthones from higher plants and 7 from fungi whereasCarpenter et al [7] listed 82 xanthones from higher plants

Gunasekera [8] recorded 183 xanthones from 5 families oftracheophyta According to Vieira and Kijjoa [9] out oftotal 515 xanthones 278 were reported from natural sourcesThese xanthones have been isolated from 20 families ofhigher plants (122 species in 44 genera) fungi (19 species)and lichens (3 species) In this period the xanthones fromhigher plants appear to be associatedmainly with the familiesClusiaceae (55 species in 12 genera) and Gentianaceae (28species in 8 genera) Bo and Liu [10] have reviewed separationmethods used for pharmacologically active xanthones JosePedraza-Chaverri et al [11] reviewed the isolated chemicalconstituents and medicinal properties of C Garcinia (man-gostana) Some of the plants ferns and fungus species whichcontain xanthones areArtocarpus Anthocleista AllanblackiaAndrographis Aspergillus Bersama Blackstonia Calophyl-lum Canscora Centaurium Chironia Cratoxylum Comas-toma Garcinia Cudrania Eustoma Emericella FraseraGarcinia Gentiana Gentianella Gentianopsis Halenia Hop-pea Hypericum Ixanthus Lomatogonium Mesua MorindaMacrocarpaea Mangrove fungi Orphium Peperomia Pen-tadesma Polygala Penicillium Phoma Phomopsis Rheedia

2 Journal of Applied Chemistry

Rhus Securidaca Symphonia Schultesia Swertia Tripteros-permum Vismia Veratrilla and Xylaria

2 Classification

Xanthones isolated fromnatural sources are classified into sixmain groups namely simple xanthones xanthone glycosidesprenylated xanthones xanthonolignoids bisxanthones andmiscellaneous xanthones

21 Simple Oxygenated Xanthones Simple oxygenated xan-thones are subdivided according to the degree of oxygenationinto non-mono- di- tri- tetra- penta- and hexaoxygenatedsubstances [9 12 13] In these xanthones the substituents aresimple hydroxymethoxy ormethyl groups About 150 simpleoxygenated xanthones have been reported

211 Nonoxygenated Simple Xanthones The nonoxygenatedxanthones namely methylxanthones (1-2-3-4-methyl-xanthone) were reported in crude oils from off-shoreNorway [14] This was the first description of xanthonesin fossil organic matter These xanthones might have beengenerated as diagenetic products formed by oxidation ofxanthenes in the reservoir or might have originated bybiosynthesis from aromatic precursors

212 Monooxygenated Xanthones Besides six monooxy-genated xanthones from Swertia 2-hydroxyxanthone4-hydroxyxanthone and 2-methoxyxanthone have beenisolated from four genera namely Calophyllum KielmeyeraMesua and Ochrocarpus

213 Dioxygenated Xanthones More than fifteen dioxygen-ated xanthones were reported from plants of the familiesClusiaceae and Euphorbiaceae 15-Dihydroxyxanthone 17-dihydroxyxanthone and 26-dihydroxyxanthone are foundfairly extensively Other deoxygenated xanthones suchas 1-hydroxy-5-methoxyxanthone 1-hydroxy-7-methox-yxanthone 2-hydroxy-1-methoxy-xanthone 3-hydrox-y-2-methoxyxanthone 3-hydroxy-4-methoxyxanthone5-hydroxy-1-methoxyxanthone and 12-methylenedioxyx-anthone have been reported from eleven plants genera

214 Trioxygenated Xanthones Forty-five trioxygenatedxanthones have been reported out of these fifteen weredescribed as new Among these only two natural sulfonatedxanthones namely 13-dihydroxy-5-methoxyxanthone-4-sulfonate and 5-O-120573-D-glucopyranosyl-13-dihydroxy-xanthone-4-sulfonate are reported from Hypericum sam-psonii These sulfonated xanthones were found to exhibitsignificant cytotoxicity against cancer cell line [15 16]135- 156- 167- and 234-trihydroxyxanthone seventeenmethyl ethers and two methylenedioxy derivatives fromnine genera have been reported

215 Tetraoxygenated Xanthones Among the 53 tetraoxy-genated xanthones identified so far 21 were found to be new

natural products These xanthones were mainly reportedfrom plants of the families Gentianaceae Clusiaceae andPolygalaceae Interestingly 7-chloro-123-trihydroxy-6-methoxyxanthone isolated from Polygala vulgaris [17]appeared to be the first chloroxanthone of the familyPolygalaceae This compound exhibited antiproliferativeactivity against the human intestinal adenocarcinoma cellline The free hydroxyxanthones are 1356- 1357- and1367-tetrahydroxyxanthone [18]

216 Pentaoxygenated Xanthones Twenty-seven pentaoxy-genated xanthones have been identified Four partiallymethylated pentaoxygenated xanthones namely 18-dihy-droxy-237-trimethoxyxanthone 56-dihydroxy-137-trime-thoxyxanthone 17-dihydroxy-238-trimethoxyxanthone38-dihydroxy-126-trimethoxyxanthone [19] and 37-dihydroxy-156-trimethoxyxanthone have been isolatedfrom three plants genera

217 Hexaoxygenated Xanthones Two hexaoxygenated xan-thones 8-hydroxy-12346-pentamethoxyxanthone [15 20]and 18-dihydroxy-2346-tetramethoxyxanthone [21] areisolated from two Centaurium species and 3-hydroxy-12567-pentamethoxyxanthone was isolated from the rootsof Polygala japonica The natural occurrence of pentaoxy-genated hexaoxygenated and dimeric xanthones has beenreviewed by Peres and Nagem [22]

22 Xanthone Glycosides Sixty-one naturally occurring gly-cosylated xanthones thirty-nine of which are new com-pounds have been reported predominantly in the familiesGentianaceae and Polygalaceae as C- or O-glycosides Thedetails of naturally occurring xanthone glycosides have beenreviewed [2] and distinction between C-glycosides and O-glycosides has also been made In C-glycosides CndashC bondlinks the sugar moiety to the xanthone nucleus and they areresistant to acidic and enzymatic hydrolysis whereas the O-glycosides have typical glycosidic linkage

221 C-Glycosides C-glycosides are rare thus only sevenC-glycosides were mentioned in Sultanbawarsquos review [13] and17 in Al-Hazimirsquos review [23] Mangiferin and isomangiferinare the most common C-glycosides Mangiferin (2-C-120573-D-glucopyranosyl-1367-tetrahydroxyxanthone) is of wide-spread occurrence in angiosperms and ferns andwas first isolated from Mangifera indica [24ndash26] Anisomer isomangiferin (4-C-120573-D-glucopyranosyl-1367-tetrahydroxyxanthone) has been isolated from the aerialparts of Anemarrhena asphodeloides [27] Homomangi-ferin (2-C-120573-D-glucopyranosyl-3-methoxy-167-trihydrox-yxanthone) has also been isolated from the bark ofMangiferaindica [28] In 1973 another glycoxanthone (2-C-120573-D-glucopyranosyl-1356-tetrahydroxyxanthone) with an oxi-dation pattern other than that of mangiferin was foundin Canscora decussate [29] Arisawa and Morita [30] haveisolated tetraoxygenated xanthone glycoside 2-C-120573-D-glucopyranosyl-5-methoxy-136-trihydroxyxanthone fromIris florentina

Journal of Applied Chemistry 3

222 O-Glycosides More than 20 xanthone O-glycosides areknown A few are from natural sources namely gentiacau-loside from Gentiana acaulis gentioside from G luteaand swertianolin from Swertia japonica [31] Their naturaloccurrence is restricted to the family Gentianaceae Thefirst xanthone O-glycoside norswertianin-1-O-glucosyl-3-O-glucoside was isolated from S perennis [2] A tetraox-ygenated xanthoneO-glycoside (378-trihydroxyxanthone-1-O-120573-laminaribioside) was isolated from the fern species [32]1-Hydroxy-7-methoxy-3-O-primeverosylxanthone [33] and1-methoxy-5-hydroxyxanthone-3-O-rutinoside [34] havebeen isolated from Gentiana species and Canscora decussata

23 Prenylated and Related Xanthones Among 285 preny-lated xanthones 173 were described as new compounds Theoccurrence of prenylated xanthones is restricted to the plantspecies of the family Guttiferae The major C

5unit of the

substituents included the commonly found 3-methylbut-2-enyl or isoprenyl group as in isoemericellin and the lessfrequent 3-hydroxy-3-methylbutyl as in nigrolineaxanthoneP and 11-dimethylprop-2-enyl as in globuxanthone respec-tively [35ndash37] Prenylated xanthones caloxanthone O andcaloxanthone P were isolated from Calophyllum inophyllum[38] and polyprenylated xanthones and benzophenones fromGarcinia oblongifolia [39]

24 Xanthonolignoids Naturally occurring xanthonolig-noids are rare so only five compounds are known Thefirst xanthonolignoid was isolated from Kielmeyera speciesby Castelao Jr et al [40] They also isolated two otherxanthonolignoids named Cadensins A and B from Caraipadensiflora A xanthonolignoid Kielcorin was obtained fromHypericum species [41] Recently kielcorin was also isolatedfrom Vismia guaramirangae [42] Kielmeyera variabilis [43]and Hypericum canariensis [44] whereas cadensin C andcadensin D from Vismia guaramirangae and Hypericumcanariensis have been reported [45]

25 Bisxanthones A total of twelve bisxanthones five fromhigher plants one from lichen and six from fungi havebeen reported to date These include jacarelhyperols A andB [46] from the aerial parts of Hypericum japonicum anddimeric xanthone and globulixanthone E from the roots ofSymphonia globulifera [47] Three C

2-C2rsquo dimeric tetrahy-

droxyxanthones dicerandrols A B and C are also isolatedfrom the fungus Phomopsis longicolla [48]

26 Miscellaneous Xanthones with substituents other thanthosementioned above are included in this group Xanthoful-vin and vinaxanthone were isolated from Penicillium species[49] A polycyclic substance (xanthopterin) with the abilityto inhibit the HSP47 (heat shock protein) gene expressionwas isolated from the culture broth of a Streptomyces species[50] Xantholiptin is a potent inhibitor of collagen productioninduced by treatment with TGF-b in human dermal fibrob-lasts Xanthones have been synthesized by different methodsThe elements of synthetic methods such as building blocks

Diels-Alder reaction and heterogeneous catalysts have alsobeen reviewed [51]

3 Methods for Isolation and Characterizationof Xanthones

Plants xanthones are commonly isolated by column chro-matography on silica gel using different solventmixtures withincreasing polarity [52ndash55] Xanthone glycosides are usuallycrystallized from MeOH They may also be separated andidentified using TLC [56] and HPLC [57ndash61] by comparisonwith authentic samples The structure of xanthones has beenestablished on the basis of UV IRMS andNMRdata [13 62ndash72] Preparative TLC on silica gel using AcOEt MeOH andH2O (21 4 3) as mobile phase has been used in instances

of difficult separation Frequently used solvents in TLC areon polyamide MeOH-H

2O (9 1) and MeOH-H

2O-AcOH

(90 5 5) on cellulose HOAc (5ndash30) on silica gel Py-H2O-AcOEt-MeOH (12 10 80 5) and AcOEt-MeOH-H

2O

(21 4 3) and chromatoplates are viewed in UV light Incertain cases sprayingwith 5KOH inMeOHor 5aqueousH2SO4has been advantageous [33] Polyamide columns are

frequently applied for the separation of xanthone glycosidesPurification of xanthones on Sephadex LH20 columnhas alsobeen carried out [2] Xanthones are also isolated from resin ofGarcinia hanburyi [73] and from the fermentation productsof an endophytic fungus Phomopsis [74]

HPLC has been proved as the best technique forseparation identification and quantification of xanthonesSeveral HPLC methods have been developed for natu-rally occurring xanthones using microporous chemicallybonded silica gel (Micropak CN column) solvent hexane-chloroform (13 7 vv) isooctane-CHCl

3(3 17 vv) or

dioxane-dichloromethane (1 9) detected at 254 nm by UVdetector [60] Polar aglycones as well as glycosides ofxanthones are also resolved on reversed phase column(C8and C

18) using acetonitrile-water as mobile phase [75

76] High-speed counter current chromatography (HSCCC)and high performance centrifugal partition chromatography(HPCPC) were also used for the separation and isola-tion of mangiferin and neomangiferin from an extract ofAnemarrhena asphodeloides [77] and 120572-mangostins and 120574-mangostins from mangosteen pericarp respectively [78]

31 Ultraviolet Visible Spectroscopy (UV) Ultraviolet visiblespectroscopy technique is useful for locating free hydroxylgroups in xanthones In particular the OH group at position3 is easily detected by addition of NaOAc which results in abathochromic shift of the 300ndash330 nm bands with increasedintensity Three or four bands of maximum absorption arealways found in the region 220ndash410 nm and it is noteworthythat all bands show high intensity Most of the substancesshow a marked absorption in the 400 nm regions whichaccounts for their yellow colour [79]

32 Infrared Spectroscopy (IR) The carbonyl group in xan-thones is always easily detectable in IR spectra as a strongband (stretching frequency) in the region of 1657 cmminus1 [53]


The presence of a hydroxyl group in the l or 8 position lowersthe frequency to about 1650 cmminus1 by hydrogen bondingSubstituents in the 3 or 6 position of the xanthone nucleusmay have a marked effect upon the carbonyl stretchingfrequency [80]33 Proton Nuclear Magnetic Resonance Spectroscopy (1HNMR) 1D and 2D-NMR spectra (1H 13C DEPT COSYTOCSY HROESY HSQC HMBC and NOESY) have beenused for characterization of the xanthones The 1H NMRspectrum appears predominantly in the range of 0ndash12 ppmdownfield from the reference signal of TMS The integral ofthe signals is proportional to the number of protons present1H NMR gives information about the substitution patternon each ring Acetylated derivatives have been utilised inthe structure determination of glycosides [81] The numberand relative position of acetyl and methoxy groups canbe determined by observing the shift for the position ofabsorption for the aromatic protons which occurs uponreplacing methoxy group by an acetyl group Signals between120575 240ndash250 are indicative of acetylation at peri-position to thecarbonyl group (1 or 8 position) since for other positions theacetyl signals fall between 120575 230 and 235 In nonacetylatedxanthones the presence of hydrogen bonded OH at 120575 12-13 also confirms hydroxyl substitution at 1 or 8 But whenthese positions are unsubstituted then absorption for thearomatic protons appears at120575 770ndash805 [82] Tetraoxygenatedxanthones namely 1378- and 1358- showed two meta-and two ortho-coupled protons in the 1H NMR spectrumThey can also be distinguished by the fact that the presencefor the ortho-coupled proton in the 1378- system appearsat lower field [83] than that for 1358- (bellidifolin) system[84] The signals of 210158401015840-O-acetyl methyl protons of 8-C-glucosyl flavone acetate are found at higher field than those ofcorresponding 6-C-glucosyl flavone acetate [85] In a similarmanner 2-C and 4-C isomeric glycosyl xanthones can bedistinguished

34 Carbon Nuclear Magnetic Resonance Spectroscopy (13CNMR) The number of signals in the 13C NMR spectrumindicates the number of different types of C atoms It gives theinformation about the total number of the C atoms present inthe molecule It is particularly diagnostic for determining thesugar linkage in di- or polysaccharides the signal of the car-bon carrying the primary alcohols appears at 120575 62 in glucoseThis signal is shifted to 120575 67 in disaccharides possessing a 1ndash6 linkage [60 61] The chemical shift for carbonyl carbon is120575 1845 when positions 1 and 8 are substituted by hydroxylgroups But when one of these positions is occupied either bya methoxy or a sugar moiety the carbonyl signal is shiftedupfield by about 4 ppm If both positions are occupied by amethoxy group or sugar moieties the upfield shift is about10 ppm When methoxy groups are located in position 1 or8 the corresponding absorption appears at 120575 60-61 whereasthey appear at about 120575 56 when the methoxy group is locatedin the remaining positions on xanthone nucleus [53]

35 Mass Spectrometry (MS) Mass spectrometry is also auseful tool in the structure elucidation of xanthone glyco-sides Prox [86] established the fragmentation pattern of

mangiferin and related C-glycosides Aritomi and Kawasaki[27 28] obtained satisfactory results using peracetylatedderivatives of the same and analogous compounds In massspectrum of O-glycosides no discernible molecular ionpeak can be observed but an important fragment ion peakdue to the aglycone moiety appears followed by furtherfragmentation Significant fragment ions from the loss ofOH H

2O and CHO are typical for xanthones and related

compounds with a methoxy substituent peri to the carbonylgroup [34 53 87]

4 Biological Activities of Xanthones

Plants belonging to the family Gentianaceae are best knownfor their bitter taste due to the presence of xanthones and areused in traditional remedies against loss of appetite and feverand are still included inmany ldquotonicrdquo formulations [88] Somespecific activities have been reported for xanthones and iri-doids from Gentianaceae Xanthones (especially mangiferin)are reported to give CNS stimulation [89 90] and haveanti-inflammatory activity [12] For bellidifolin and swer-chirin a strong hypoglycemic activity has been reported[91ndash93] A crude extract of Swertia has been reported todisplay insect repellent activity [94] The extracts of mostof the Swertia species show mutagenic activity [95] Anextract from S paniculata is used in the Indian System ofMedicine as a bitter tonic and in the treatment of somemental disorders [96] S hookeri extract is used in thetreatment ofmicrobial infections and as amood elevator [97]Swertifrancheside isolated from S franchetiana was foundto be potent inhibitor of the DNA polymerase activity ofhuman immunodeficiency virus-1 reverse transcriptase [98]Naturally occurring xanthones have emerged as an importantclass of organic compounds in view of their remarkablepharmacological and other biological activities It has nowbeen observed that a number of plant products which arein regular use as chemotherapeutic agents contain xanthonesas active constituents Mangiferin was the first xanthone tobe investigated pharmacologically and has been found toexhibit a broad spectrum of biological activities It showsmonoamine oxidase inhibition cardiotonic convulsant andcholeretic activities [29 89] Pronounced anti-inflammatoryactivity has also been observed for mangiferin [99] Oraland topical compounds containing mangiferin are useful forthe treatment of diseases caused by herpes virus Mangiferinhas been found to protect the liver of the rats from highaltitude hypoxia On the other hand Ghosal and Chaudhuri[100] have observed the opposite CNS depressant effect forxanthone-O-glycosides in mice and rats The antimalarialdrug AYUSH-64 contains S chirata as one of the ingredientsXanthones from S chirata are reported to produce CNSdepression [29] The total extract of S chirata showed signif-icant antifeedant activity against Jute semilooper [101] Nor-swertianolin an O-glycoside has been reported to produceantitubercular activity The O-glycosides of S purpurascensare known to produceCNSdepression in albino rats andmice[102] Xanthones ofMammea americana exhibited inhibitory


COOHHO COOH

O

HO

O O

OHO

O

OHOH

OH

HO

O

HO

OH

OHHO

OHO

O

OH

OH

O

O OH

(2) (1) 135-trihydroxyxanthone

Shikimate-acetate intermediate

Three acetate unitsNH2

23998400 46-tetrahydroxybenzophenone

R998400998400O

OR998400

R998400= H R998400998400

= H gentisinR998400

= Me R998400998400= H gentisin

R998400= H R998400998400

= Me isogentisin

Figure 1 Biosynthetic pathways leading to the xanthones (1) and (2)

activity against sarcoma 180 tumor cell [103] 18-Dihydroxy-35-dimethoxyxanthone (swerchirin) isolated from the hex-ane fraction from Swertia chirayita has a very significantblood sugar lowering effect in fasted fed glucose loadedand tolbutamide pretreated albino rats The ED

50for 40

glycaemia lowering in CF male albino rats was 231mgkgwhen orally administered [104] Swertia species have alsobeen investigated for the presence of essential elements [105ndash107] Xanthones have been reported to display hepatoprotec-tive antimicrobial anticarcinogenic antileprosy antioxidantanticholinergic mutagenicity [108 109] and radioprotec-tive effect [110] immunomodulatory effect [111] antiboneresorption [112] and antiparasitic effects [113] neuraminidaseinhibitory [114] antimalarial [115] anticomplement [116]antifungal and algicidal [117] and anti-HIV activity [118]and cardioprotective antitumoral antibacterial antidia-betes antihyperlipidemic antiatherogenic immunomodula-tor anti-inflammatory antiulcer antiviral antifungal [119]antidiabetic hypolipidemic [120] analgesic antiasthmaticantihistaminic antiamoebic diuretic antidiarrheal larvici-dal ovicidal antiprotozoal antileptospiral anti-TMV andanticancer activities [121ndash124] Xanthones from S mussotiiwere evaluated for their anti-hepatitis B virus activity onHepG 2215 cells line they exhibited significant activityinhibiting hepatitis B virus DNA replication with IC

50values

from 001mM to 013mM [125]

5 Biosynthesis of Xanthones

Biosynthetically xanthones are of mixed shikimate andacetate origin (Figure 1) Thus phenylalanine which isformed from shikimate loses two carbon atoms from theside-chain and is oxidized to form m-hydroxybenzoic acidThis combines with three units of acetate (via malonate)to give the intermediate The shikimate-acetate intermediateundergoes ring-closure to give substituted benzophenonewhich by an oxidative phenol coupling generates the centralring of the xanthone moiety This oxidative coupling cantake place in two ways depending on the folding of thebenzophenone either in the ortho or in the para positionto the hydroxyl substituent in the potential B-ring to give135-trihydroxyxanthone (1) or the 137-substituted analoguegentisin (2) respectively Thus depending on the orientationof the intermediate two different hydroxylation patterns canbe found Experimental proof for the overall pathway hasbeen obtained from experiments performed using Gentianalutea [126 127]

When plants were fed 14C-labeled phenylalanine thelabelwas recovered solely in theB-ring (Figure 1) Converselyfeeding of 14C-labeled acetate gave incorporation of the mainpart in the A-ring The alternative ring closure to (1) hasrecently been shown to take place in cultured cells of Centau-rium erythraea where 23101584046-tetrahydroxybenzophenone


is the precursor for 135-trihydroxyxanthone [128] Fur-thermore in these cell cultures compound (1) is selec-tively oxidized by a xanthone 6-hydroxylase to 1356-tetrahydroxyxanthone [129] Explored methods for synthesisof simple oxygenated xanthones have been documented bySousa and Pinto [130]

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are thankful to Director HRDI and ProfessorM S M Rawat Dean School of Sciences HNB GarhwalUniversity Srinagar Uttarakhand India

References

[1] M L Cardona I Fernandez J R Pedro and A SerranoldquoXanthones fromHypericum reflexumrdquo Phytochemistry vol 29no 9 pp 3003ndash3006 1990

[2] K Hostettmann and I Miura ldquoA new Xanthone diglucosidefrom Swertia perennis Lrdquo Helvetica Chimica Acta vol 60 pp262ndash264 1977

[3] K M Hostettmann K Hostettmann and O Sticher ldquoXan-thones flavones and secoiridoids of americanGentiana speciesrdquoPhytochemistry vol 20 no 3 pp 443ndash446 1981

[4] J C Roberts ldquoNaturally occurring xanthonesrdquo ChemicalReviews vol 61 no 6 pp 591ndash605 1961

[5] F M Dean Naturally Occurring Oxygen Ring CompoundsButterworth London UK 1963

[6] O R Gottlieb ldquoBiogenetic proposals regarding aucuparins andxanthonesrdquo Phytochemistry vol 7 no 3 pp 411ndash421 1968

[7] I Carpenter H D Locksley and F Scheinmann ldquoXanthonesin higher plants biogenetic proposals and a chemotaxonomicsurveyrdquo Phytochemistry vol 8 no 10 pp 2013ndash2025 1969

[8] S P Gunasekera University of Sri Lanka Peradeniya CampusPeradeniya Sri Lanka 1976

[9] L M M Vieira and A Kijjoa ldquoNaturally-occurring xanthonesrecent developmentsrdquo Current Medicinal Chemistry vol 12 no21 pp 2413ndash2446 2005

[10] T Bo and H Liu ldquoSeparation methods for pharmacologicallyactive xanthonesrdquo Journal of Chromatography B vol 812 no 1-2 pp 165ndash174 2004

[11] J Pedraza-Chaverri N Cardenas-Rodrıguez M Orozco-Ibarra and J M Perez-Rojas ldquoMedicinal properties of man-gosteen (Garcinia mangostana)rdquo Food and Chemical Toxicologyvol 46 no 10 pp 3227ndash3239 2008

[12] S Mandal P C Das and P C Joshi ldquoNaturally occuringxanthones from terrestrial florardquo Journal of Indian ChemicalSociety vol 69 pp 611ndash636 1992

[13] M U S Sultanbawa ldquoXanthonoids of tropical plantsrdquo Tetrahe-dron vol 36 no 11 pp 1465ndash1506 1980

[14] T B P Oldenburg H Wilkes B Horsfield A C T Van DuinD Stoddart and A Wilhelms ldquoXanthonesmdashnovel aromaticoxygen-containing compounds in crude oilsrdquo Organic Geo-chemistry vol 33 no 5 pp 595ndash609 2002

[15] T Jankovic D Krstic K Savikin-Fodulovic N Menkovicand D Grubisic ldquoXanthones and secoiridoids from hairy rootcultures of Centaurium erythraea and C pulchellumrdquo PlantaMedica vol 68 no 10 pp 944ndash946 2002

[16] M-J Don Y-J Huang R-L Huang and Y-L Lin ldquoNewphenolic principles from Hypericum sampsoniirdquo Chemical andPharmaceutical Bulletin vol 52 no 7 pp 866ndash869 2004

[17] S DallrsquoAcqua G Innocenti G Viola A Piovan R Caniatoand E M Cappelletti ldquoCytotoxic compounds from Polygalavulgarisrdquo Chemical and Pharmaceutical Bulletin vol 50 no 11pp 1499ndash1501 2002

[18] Y Chen G K Wang C Wu and M J Qin ldquoChemicalconstituents of Gentiana rhodanthardquo Zhongguo Zhong Yao ZaZhi vol 38 no 3 pp 362ndash365 2013

[19] Q-C Xue C-J Li L Zuo J-Z Yang and D-M Zhang ldquoThreenew xanthones from the roots of Polygala japonica houttrdquoJournal of Asian Natural Products Research vol 11 no 5 pp465ndash469 2009

[20] P Valentao P B Andrade E Silva et al ldquoMethoxylatedxanthones in the quality control of small centaury (Centauriumerythraea) flowering topsrdquo Journal of Agricultural and FoodChemistry vol 50 no 3 pp 460ndash463 2002

[21] D Krstic T Jankovic K Savikin-Fodulovic N Menkovicand A Grubisic ldquoSecoiridoids and xanthones in the shootsand roots of Centaurium pulchellumcultured in-vitrordquo In VitroCellular and Developmental Biology vol 39 pp 203ndash207 2003

[22] V Peres and T J Nagem ldquoNaturally occurring pentaoxy-genated hexaoxygenated and dimeric xanthones a literaturesurveyrdquo Quimica Nova vol 20 no 4 pp 388ndash397 1997

[23] H M G Al-Hazimi and G A Miana ldquoNaturally occuringxanthones in higher plants and fernsrdquo Journal of the ChemicalSociety of Pakistan vol 12 no 2 pp 174ndash188 1990

[24] S Iseda ldquoIsolation of 1367-tetrahydroxyxanthone and theskeletal structure ofMangiferinrdquoBulletin of theChemical Societyof Japan vol 30 pp 625ndash629 1957

[25] L J Haynes and D R Taylor ldquoC-glycosyl compounds PartV Mangiferin the nuclear magnetic resonance spectra ofxanthonesrdquo Journal of the Chemical Society C pp 1685ndash16871966

[26] VK Bhatia J D Ramanathan andT R Seshadri ldquoConstitutionof mangiferinrdquo Tetrahedron vol 23 no 3 pp 1363ndash1368 1967

[27] M Aritomi and T Kawasaki ldquoA New xanthone C-glucosideposition isomer of Mangiferin from Anemarrhena asphode-loides BungerdquoChemical and Pharmaceutical Bullelin vol 18 pp2327ndash2333 1970

[28] M Aritomi and T Kawasaki ldquoA Mangiferin monomethylether from Mangifera indica Lrdquo Chemical and PharmaceuticalBullelin vol 18 pp 2224ndash2234 1970

[29] S Ghosal and R K Chaudhuri ldquoNew tetraoxygenated xan-thones of Canscora decussatardquo Phytochemistry vol 12 no 8 pp2035ndash2038 1973

[30] M Arisawa and N Morita ldquoStudies on constituents of genusIris VII The constituents of Iris unguicularis POIR (I)rdquoChemical and Pharmaceutical Bulletin vol 24 no 4 pp 815ndash817 1976

[31] V Plouvier J Massicot and P Rivaille ldquoOn gentiacauleinea new tetra-substituted xanthone aglycone of gentiacaulosideof Gentiana acaulis Lrdquo Comptes Rendus Hebdomadaires desSeances de lrsquoAcademie des Sciences D vol 264 no 9 pp 1219ndash1222 1967


[32] F Imperato ldquoA xanthone-O-glycoside from Aspleniumadiantum-nigrumrdquo Phytochemistry vol 19 no 9 pp 2030ndash2031 1980

[33] A M Verney and A M Debelmas ldquoXanthones of Gentianalutea G purpurea G punctata G pannonicardquo Annales Phar-maceutiques Francaises vol 31 pp 415ndash420 1973

[34] S Ghosal R B P S Chauhan K Biswas and R K ChaudhurildquoNew 135-trioxygenated xanthones in Canscora decussatardquoPhytochemistry vol 15 no 6 pp 1041ndash1043 1976

[35] G Bringmann G Lang S Steffens E Gunther and K Schau-mann ldquoEvariquinone isoemericellin and stromemycin froma sponge derived strain of the fungus Emericella variecolorrdquoPhytochemistry vol 63 no 4 pp 437ndash443 2003

[36] L H D Nguyen and L J Harrison ldquoXanthones and triter-penoids from the bark of Garcinia vilersianardquo Phytochemistryvol 53 no 1 pp 111ndash114 2000

[37] V Rukachaisirikul M Kamkaew D Sukavisit S PhongpaichitP Sawangchote and W C Taylor ldquoAntibacterial Xanthonesfrom the Leaves of Garcinia nigrolineatardquo Journal of NaturalProducts vol 66 no 12 pp 1531ndash1535 2003

[38] H-F Dai Y-B Zeng Q Xiao Z Han Y-X Zhao and W-LMei ldquoCaloxanthones O and P two new prenylated xanthonesfromCalophyllum inophyllumrdquoMolecules vol 15 no 2 pp 606ndash612 2010

[39] W G Shan T S Lin H N Yu Y Chen and Z J ZhanldquoPolyprenylated Xanthones and Benzophenones from the Barkof Garcinia oblongifoliardquo Helvetica Chimica Acta vol 95 no 8pp 1442ndash1448 2012

[40] J F Castelao Jr O R Gottlieb R A De Lima A A LMesquita H E Gottliebb and E Wenkert ldquoXanthonolignoidsfrom Kielmeyera and Caraipa species-13C NMR spectroscopyof xanthonesrdquo Phytochemistry vol 16 no 6 pp 735ndash740 1977

[41] H Nielsen and P Arends ldquoStructure of the xanthonolignoidkielcorinrdquo Phytochemistry vol 17 no 11 pp 2040ndash2041 1978

[42] F D Monache M M Mac-Quhae G D Monache G B MBettolo and R A De Lima ldquoXanthones xanthonolignoidsand other constituents of the roots of Vismia guaramirangaerdquoPhytochemistry vol 22 no 1 pp 227ndash232 1983

[43] L Pinheiro C V Nakamura B P Dias Filho A G Ferreira MCM Young andDAGarcia Cortez ldquoAntibacterial Xanthonesfrom Kielmeyera variabilis Mart (Clusiaceae)rdquo Memorias doInstituto Oswaldo Cruz vol 98 no 4 pp 549ndash552 2003

[44] M L Cardona M I Fernandez J R Pedro E Seoane and RVidal ldquoAdditional new xanthones and xanthonolignoids fromHypericum canariensisrdquo Journal of Natural Products vol 49 no1 pp 95ndash100 1986

[45] G G Nikolaeva V I Glyzin M S Mladentseva V I She-ichenko and A V Patudin ldquoXanthones of Gentiana luteardquoChemistry ofNatural Compounds vol 19 no 1 pp 106ndash107 1983

[46] K Ishiguro S Nagata H Oku and Y Masae ldquoBisxan-thones from Hypericum japonicum inhibitors of PAF-inducedhypotensionrdquo Planta Medica vol 68 no 3 pp 258ndash261 2002

[47] A E Nkengfack P Mkounga M Meyer Z T Fomum andB Bodo ldquoGlobulixanthones C D and E three prenylatedxanthones with antimicrobial properties from the root bark ofSymphonia globuliferardquo Phytochemistry vol 61 no 2 pp 181ndash187 2002

[48] M M Wagenaar and J Clardy ldquoDicerandrols new antibioticand cytotoxic dimers produced by the fungus Phomopsis longi-colla isolated from an endangered mintrdquo Journal of NaturalProducts vol 64 no 8 pp 1006ndash1009 2001

[49] K Kumagai N Hosotani K Kikuchi T Kimura and I SajildquoXanthofulvin a novel semaphorin inhibitor produced by astrain of Penicilliumrdquo The Journal of Antibiotics vol 56 no 7pp 610ndash616 2003

[50] Y Terui C Yiwen L Jun-Ying et al ldquoXantholipin a novelinhibitor of HSP47 gene expression produced by Streptomycessprdquo Tetrahedron Letters vol 44 no 29 pp 5427ndash5430 2003

[51] C Yang M A Li W E I Zhen-ping H A N Feng and GA O Jing ldquoAdvances in isolation and synthesis of xanthonederivativesrdquo Chinese Herbal Medicines vol 4 no 2 pp 87ndash1022012

[52] J B Harbirbe Phytochemical Methods Chapman and HallLondon UK 1973

[53] O Purev K Oyun G Odontuya et al ldquoIsolation and structureelucidation of two new xanthones from Gentiana azuriumBunge (Fam Gentianaceae)rdquo Zeitschrift fur Naturforschung Bvol 57 no 3 pp 331ndash334 2002

[54] A Khan M Rahman and S Islam ldquoIsolation and bioactivityof a xanthone glycoside from Peperomia pellucidardquo Life Sciencesand Medicine Research pp 1ndash15 2010

[55] V K Dua V P Ojha R Roy et al ldquoAnti-malarial activityof some xanthones isolated from the roots of Andrographispaniculatardquo Journal of Ethnopharmacology vol 95 no 2-3 pp247ndash251 2004

[56] H M Chawla S S Chibber and U Khera ldquoSeparationand identification of some hydroxyxanthones by thin-layerchromatographyrdquo Journal of Chromatography A vol 111 no 1pp 246ndash247 1975

[57] S Suryawanshi N Mehrotra R K Asthana and R C GuptaldquoLiquid chromatographytandemmass spectrometric study andanalysis of xanthone and secoiridoid glycoside composition ofSwertia chirata a potent antidiabeticrdquo Rapid Communicationsin Mass Spectrometry vol 20 no 24 pp 3761ndash3768 2006

[58] Y Song F Hu P Lin Y Lu and Z Shi ldquoDeterminationof xanthones in Swertia mussotii and Swertia franchetiana byhigh performance liquid chromatographyrdquo Chinese Journal ofChromatography vol 22 no 1 pp 51ndash53 2004

[59] J-S Zhang X-M Wang X-H Dong H-Y Yang and G-P LildquoStudies on chemical constituents of Swertia mussotiirdquo ZhongYao Cai vol 32 no 4 pp 511ndash514 2009

[60] J S Negi and P Singh ldquoHPLC fingerprinting of highly demand-ing medicinal plant Swertia an overviewrdquo International Journalof Medicinal and Aromatic Plants vol 1 no 3 pp 333ndash337 2011

[61] J S Negi P Singh G J Pant and M S M Rawat ldquoRP-HPLCanalysis and antidiabetic activity of Swertia paniculatardquoNaturalProduct Communications vol 5 no 6 pp 907ndash910 2010

[62] R R Sun F P Miao J Zhang G Wang X L Yin and N YJi ldquoThree new xanthone derivatives from an algicolous isolateof Aspergillus wentiirdquoMagnetic Resonance in Chemistry vol 51no 1 pp 65ndash68 2013

[63] H H F Koolen L S Menezes M P Souza et al ldquoTalarox-anthone a novel xanthone dimer from the endophytic fungusTalaromyces sp associated with Duguetia stelechanthan (Diels)R E Friesrdquo Journal of the Brazilian Chemical Society vol 24 no5 pp 880ndash883 2013

[64] A K Chakravarty T Sarkar K Masuda et al ldquoStructureand synthesis of glycoborine a new carbazole alkaloid fromthe roots of Glycosmis arborea a note on the structure ofglycozolicinerdquo Indian Journal of Chemistry B vol 40 no 6 pp484ndash489 2001

[65] S Mandal and A Chatterjee Seminar on Research in Ayurvedaand Siddha CCRAS New Delhi India 1994


[66] A K Chakravarty S Mukhopadhyay S K Moitra and BDas ldquo(-)-Syringaresinol a hepatoprotective agent and otherconstituents from Swertia chiratardquo Indian Journal of Chemistryvol 33 pp 405ndash408 1994

[67] K S Khetwal and R S Bisht ldquoA xanthone glycoside fromSwertia speciosardquo Phytochemistry vol 27 no 6 pp 1910ndash19111988

[68] D LVerma andK S Khetwal ldquoPhenolics in the roots of SwertiapaniculataWallrdquo Science and Culture vol 51 pp 305ndash306 1985

[69] M Kikuchi and M Kikuchi ldquoStudies on the constituents ofSwertia japonicaMAKINO I On the structures of new secoiri-doid diglycosidesrdquo Chemical and Pharmaceutical Bulletin vol52 no 10 pp 1210ndash1214 2004

[70] H Yang C Ding Y Duan and J Liu ldquoVariation of activeconstituents of an important Tibet folk medicine Swertiamussotii Franch (Gentianaceae) between artificially cultivatedand naturally distributedrdquo Journal of Ethnopharmacology vol98 no 1-2 pp 31ndash35 2005

[71] S-S Wang W-J Zhao X-W Han and X-M Liang ldquoTwonew iridoid glycosides from the Tibetan folk medicine SwertiafranchetianardquoChemical and Pharmaceutical Bulletin vol 53 no6 pp 674ndash676 2005

[72] H Hajimehdipour Y Amanzadeh S E Sadat Ebrahimi andVMozaffarian ldquoThree tetraoxygenated xanthones from Swertialongifoliardquo Pharmaceutical Biology vol 41 no 7 pp 497ndash4992003

[73] Y X Deng T Guo Z Y Shao H Xie and S L Pan ldquoThree newxanthones from the resin of Garcinia hanburyirdquo Planta Medicavol 79 no 9 pp 792ndash796 2013

[74] H Y Yang Y H Gao D Y Niu et al ldquoXanthone derivativesfrom the fermentation products of an endophytic fungusPhomopsis sprdquo Fitoterapia vol S0367-326X no 13 pp 00239ndash00246 2013

[75] A Aberham S Schwaiger H Stuppner and M GanzeraldquoQuantitative analysis of iridoids secoiridoids xanthones andxanthone glycosides inGentiana lutea L roots by RP-HPLC andLC-MSrdquo Journal of Pharmaceutical andBiomedical Analysis vol45 no 3 pp 437ndash442 2007

[76] R Dai J Gao and K Bi ldquoHigh-performance liquid chromato-graphic method for the determination and pharmacokineticstudy of mangiferin in plasma of rats having taken the tradi-tional Chinese medicinal preparation Zi-Shen Pillrdquo Journal ofChromatographic Science vol 42 no 2 pp 88ndash90 2004

[77] T T Zhou Z Y Zhu CWang et al ldquoOn-line puritymonitoringin high-speed counter-current chromatography applicationof HSCCC-HPLC-DAD for the preparation of 5-HMF neo-mangiferin and mangiferin from Anemarrhena asphodeloidesBungerdquo Journal of Pharmaceutical and Biomedical Analysis vol44 no 1 pp 96ndash100 2007

[78] Y Shan and W Zhang ldquoPreparative separation of majorxanthones from mangosteen pericarp using highperformancecentrifugal partition chromatographyrdquo Journal of SeparationScience vol 33 no 9 pp 1274ndash1278 2010

[79] K S Van and B Nessler ldquoUeber einige oxyxanthonerdquo Chemis-che Berichte vol 24 pp 3980ndash3984 1891

[80] W E Whitman and L A Wiles ldquoThe polarographic reductionof xanthone and methoxyxanthonesrdquo Journal of ChemicalSociety pp 3016ndash3019 1956

[81] D Barraclough H D Locksley F Scheinmann M TaveiraMagalhaes andO RGottlieb ldquoApplications of protonmagneticresonance spectroscopy in the structural investigation of xan-thonesrdquo Journal of the Chemical Society B pp 603ndash612 1970

[82] M Kaldas K Hostettmann and A Jacot-Guillarmod ldquoCon-tribution a la phytochimie du genre Gentiana IX Etude decomposes flavoniques et xanthoniques dans les feuilles deGentiana campestris L 1ere communicationrdquoHelvetica ChimicaActa vol 57 pp 2557ndash2561 1974

[83] K Hostettmann R Tabacchi and A Jacot-Guillarmod ldquoCon-tribution a la phytochimie du genre Gentiana VI Etude desxanthones dans les feuilles de Gentiana bavarica Lrdquo HelveticaChimica Acta vol 57 pp 294ndash301 1974

[84] B Gentili and R M Horowitz ldquoFlavonoids of Citrus IXSome new c-glycosylflavones and a nuclear magnetic resonancemethod for differentiating 6- and 8-c-glycosyl isomersrdquo Journalof Organic Chemistry vol 33 no 4 pp 1571ndash1577 1968

[85] D K Holdsworth ldquoA method to differentiate isomeric C-glucosyl chromones isoflavones and xanthonesrdquo Phytochem-istry vol 12 no 8 pp 2011ndash2015 1973

[86] A Prox ldquoMassenspektrometrische untersuchung einigernaturlicher C-glukosyl-verbindungenrdquo Tetrahedron vol 24no 9 pp 3697ndash3715 1968

[87] P Arends P Helboe and Moller ldquoMass spectrometry ofxanthones-I the electron-impact-induced fragmentation ofxanthone monohydroxy and monomethoxyxanthonesrdquo Jour-nal of Organic Mass Spectrometry vol 7 pp 667ndash681 1998

[88] B Martindale The Extra Pharmacopoeia The PharmaceuticalPress London UK 28th edition 1982

[89] S K Bhattacharya SGhosal R KChaudhuri andAK SanyalldquoCanscora decussata (Gentianaceae) xanthones 3 Pharmaco-logical studiesrdquo Journal of Pharmaceutical Sciences vol 61 no11 pp 1838ndash1840 1972

[90] C N LinM I ChungM ArisawaM Shimizu andNMoritaldquoThe constituents of Tripterospermum taiwanense Satake varalpinum Satake and pharmacological activity of some xanthonederivativesrdquo Shoyakugaku Zasshi vol 38 pp 80ndash82 1984

[91] A M Saxena M B Bajpai P S R Murthy and S K Mukher-jee ldquoMechanism of blood sugar lowering by a swerchirin-containing hexane fraction (SWI) of Swertia chirayitardquo IndianJournal of Experimental Biology vol 31 no 2 pp 178ndash181 1993

[92] P Basnet S Kadota T Namba and M Shimizu ldquoThe hypo-glycaemic activity of Swertia japonica extract in streptozotocininduced hyperglycaemic ratsrdquo Phytotherapy Research vol 8 no1 pp 55ndash57 1994

[93] P Basnet S Kadota M Shimizu Y Takata M Kobayashiand T Namba ldquoBellidifolin stimulates glucose uptake in rat1 fibroblasts and ameliorates hyperglycemia in streptozotocin(STZ)-induced diabetic ratsrdquo Planta Medica vol 61 no 5 pp402ndash405 1995

[94] T Okada ldquoInsect repellantrdquo Japan Patent 7875 327 (ChemicalAbstract no 89 192516 (1978)) 1977

[95] I Morimoto F Watanabe and T Osawa ldquoMutagenicityscreening of crude drugs with Bacillus subtilis rec-assay andSalmonellamicrosome reversion assayrdquoMutation Research vol97 no 2 pp 81ndash102 1982

[96] A Prakash P C Basumatary S Ghosal and S S HandaldquoChemical constituents of Swertia paniculatardquo Planta Medicavol 45 no 1 pp 61ndash62 1982

[97] S Ghosal K Biswas and D K Jaiswal ldquoXanthone and flavonolconstituents of Swertia hookerirdquo Phytochemistry vol 19 no 1pp 123ndash126 1980

[98] T Pengsuparp L Cai H Constant et al ldquoMechanistic evalua-tion of newplant-derived compounds that inhibitHIV-1 reversetranscriptaserdquo Journal of Natural Products vol 58 no 7 pp1024ndash1031 1995


[99] P C Das S Sarkar A Das et al Proceeding of the 5th ISHSInternational Symposium on Medicinal Aromatic and SpicePlants Darjeeling India 1985

[100] S Ghosal and R K Chaudhuri ldquoChemical constituents of gen-tianaceae XVI antitubercular activity of xanthones of Canscoradecussata Schultrdquo Journal of Pharmaceutical Sciences vol 64no 5 pp 888ndash889 1975

[101] R N Mullick P C Das and S M Chatterji ldquoAntifeedingproperties of Swerita chirata against jute semilooper (Anomissabulifera Guen)rdquo Current Science vol 54 pp 1110ndash1112 1985

[102] S Ghosal P V Sharma and R K Chaudhuri ldquoChemicalconstituents of gentianaceae X xanthone O glucosides ofSwertia purpurascensWallrdquo Journal of Pharmaceutical Sciencesvol 63 no 8 pp 1286ndash1290 1974

[103] R A Finnegan K E Merkel and J K Patel ldquoConstituents ofMammea americana L XII Biological data for xanthones andbenzophenonesrdquo Journal of Pharmaceutical Sciences vol 62 no3 pp 483ndash485 1973

[104] M B Bajpai R K Asthana N K Sharma S K Chatterjee andS K Mukherjee ldquoHypoglycemic effect of swerchirin from thehexane fraction of Swertia chirayitardquo Planta Medica vol 57 no2 pp 102ndash104 1991

[105] J S Negi P Singh G J Nee Pant andM SM Rawat ldquoStudy onthe variations ofmineral elements in Swertia speciosa (G Don)rdquoBiological Trace Element Research vol 138 no 1ndash3 pp 300ndash3062010

[106] J S Negi ldquoEvaluation of trace element contents in SwertiapaniculataWallrdquoNatural Product Research vol 26 no 1 pp 72ndash76 2012

[107] J S Negi P Singh M S M Rawat and G J Pant ldquoStudyon the trace elements in Swertia chirayita (Roxb) H KarstenrdquoBiological Trace Element Research vol 133 no 3 pp 350ndash3562010

[108] J S Negi P Singh and B Rawat ldquoChemical constituents andbiological importance of Swertia a reviewrdquo Current Research inChemistry vol 3 no 1 pp 1ndash15 2011

[109] C T Luo S S Mao F L Liu et al ldquoAntioxidant xanthones fromSwertia mussotii a high altitude plantrdquo Fitoterapia vol S0367-326X no 13 pp 00229ndash00233 2013

[110] G C Jagetia and V A Venkatesha ldquoMangiferin a glucosylxan-thone protects against the radiation-induced micronuclei for-mation in the cultured human peripheral blood lymphocytesrdquoInternational Congress Series vol 1276 pp 195ndash196 2005

[111] J Leiro J A Arranz M Yanez F M Ubeira M L Sanmartınand F Orallo ldquoExpression profiles of genes involved in themouse nuclear factor-kappa B signal transduction pathway aremodulated by mangiferinrdquo International Immunopharmacol-ogy vol 4 no 6 pp 763ndash778 2004

[112] H Li T Miyahara Y Tezuka et al ldquoThe effect of Kampoformulae on bone resorption in vitro and in vivo I Activeconstituents of Tsu-kan-ganrdquo Biological and PharmaceuticalBulletin vol 21 no 12 pp 1322ndash1326 1998

[113] S Perrucci G Fichi C Buggiani G Rossi and G FlaminildquoEfficacy of mangiferin against Cryptosporidium parvum in aneonatal mousemodelrdquo Parasitology Research vol 99 no 2 pp184ndash188 2006

[114] H W Ryu M J Curtis-Long S Jung et al ldquoXanthoneswith neuraminidase inhibitory activity from the seedcases ofGarciniamangostanardquoBioorganic andMedicinal Chemistry vol18 no 17 pp 6258ndash6264 2010

[115] MV Ignatushchenko RWWinter andM Riscoe ldquoXanthonesas antimalarial agents sage specificityrdquoTheAmerican Journal ofTropical Medicine and Hygiene vol 62 no 1 pp 77ndash81 2000

[116] G-H Quan S-R Oh J-H Kim H-K Lee A D Kinghornand Y-W Chin ldquoXanthone constituents of the fruits ofGarcinia mangostanawith anticomplement activityrdquo Phytother-apy Research vol 24 no 10 pp 1575ndash1577 2010

[117] F M Tala K Krohn H Hussain et al ldquoLaurentixanthone C anew antifungal and algicidal xanthone from stembark ofVismialaurentiirdquo Zeitschrift fur Naturforschung B vol 62 no 4 pp565ndash568 2007

[118] A Groweiss J H Cardellina II and M R Boyd ldquoHIV-inhibitory prenylated xanthones and flavones from Macluratinctoriardquo Journal of Natural Products vol 63 no 11 pp 1537ndash1539 2000

[119] M M M Pinto M E Sousa and M S J NascimentoldquoXanthone derivatives new insights in biological activitiesrdquoCurrent Medicinal Chemistry vol 12 no 21 pp 2517ndash25382005

[120] B Dineshkumar A Mitra and M Manjunatha ldquoStudies onthe anti-diabetic and hypolipidemic potentials of mangiferin(xanthone glucoside) in streptozotocin-induced type 1 and type2 diabetic model ratsrdquo International Journal of Advances inPharmaceutical Sciences vol 1 no 1 pp 75ndash85 2010

[121] T Shan Q Ma K Guo et al ldquoXanthones from mangosteenextracts as natural chemopreventive agents potential anticancerdrugsrdquo Current Molecular Medicine vol 11 no 8 pp 666ndash6772011

[122] W Seesom A Jaratrungtawee S Suksumran et al ldquoAntilep-tospiral activity of xanthones from Garcinia mangostana andsynergy of gamma-mangostin with penicillin Grdquo BMCComple-mentary and Alternative Medicine vol 13 no 1 p 182 2013

[123] S M Al-Massarani A A El Gamal N M Al-Musayeib etal ldquoPhytochemical antimicrobial and antiprotozoal evaluationof Garcinia mangostana pericarp and a-mangostin its majorxanthone derivativerdquoMolecules vol 18 no 9 pp 10599ndash106082013

[124] Y P Wu W Zhao Z Y Xia et al ldquoThree novel xanthones fromGarcinia paucinervis and their anti-TMV activityrdquo Moleculesvol 18 no 8 pp 9663ndash9669 2013

[125] T W Cao C A Geng Y B Ma et al ldquoXanthones with anti-hepatitis B virus activity from Swertia mussotiirdquo Planta Medicavol 79 no 8 pp 697ndash700 2013

[126] J E Atkinson P Gupta and J R Lewis ldquoBenzophenone par-ticipation in xanthone biosynthesis (Gentianaceae)rdquo ChemicalCommunications no 22 pp 1386ndash1387 1968

[127] P Gupta and J R Lewis ldquoBiogenesis of xanthones in Gentianaluteardquo Journal of the Chemical Society C pp 629ndash631 1971

[128] S Peters W Schmidt and L Beerhues ldquoRegioselective oxida-tive phenol couplings of 23rsquo46-tetrahydroxybenzophenone incell cultures of Centaurium erythraea RAFN and Hypericumandrosaemum Lrdquo Planta vol 204 no 1 pp 64ndash69 1998

[129] W Schmidt S Peters and L Beerhues ldquoXanthone 6-hydroxylase from cell cultures of Centaurium erythraea RAFNandHypericum androsaemum Lrdquo Phytochemistry vol 53 no 4pp 427ndash431 2000

[130] M E Sousa and M M M Pinto ldquoSynthesis of xanthonesan overviewrdquo Current Medicinal Chemistry vol 12 no 21 pp2447ndash2479 2005

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Hindawi Publishing CorporationJournal of Applied ChemistryVolume 2013 Article ID 621459 9 pageshttpdxdoiorg1011552013621459

Review ArticleNaturally Occurring Xanthones Chemistry and Biology

J S Negi1 V K Bisht1 P Singh2 M S M Rawat2 and G P Joshi2

1 Herbal Analytical Laboratory Herbal Research and Development Institute Mandal Gopeshwar Uttarakhand 246401 India2Department of Chemistry HNB Garhwal University Srinagar Garhwal Uttarakhand 246174 India

Correspondence should be addressed to J S Negi negijsyahoocom

Received 4 April 2013 Accepted 24 September 2013

Academic Editor Ming-Jer Lee

Copyright copy 2013 J S Negi et alThis is an open access article distributed under the Creative Commons Attribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Xanthones are one of the biggest classes of compounds in natural product chemistry A number of xanthones have been isolatedfrom natural sources of higher plants fungi ferns and lichens They have gradually risen to great importance because of theirmedicinal properties This review focuses on the types isolation characterization biological applications and biosynthesis ofnaturally occurring xanthones isolated so far Different physicochemical and instrumental methods such as liquid-solid andliquid-liquid extraction TLC flash chromatography column chromatography IR 1H NMR and 13C NMR spectroscopy GLCHPLC GC and LCMS have been widely used for isolation and structural elucidation of xanthones Hepatoprotective anti-carcinogenic antileprosy antimalarial antioxidant anticholinergic mutagenicity radioprotective immunomodulatory antiboneresorption antiparasitic neuraminidase inhibitory anticomplement antibacterial antifungal algicidal anti-HIV cardioprotectiveantitumoral antidiabetes antihyperlipidemic antiatherogenic anti-inflammatory antiulcer antidiabetic hypolipidemic analgesicantiasthmatic antihistaminic antiamoebic diuretic antidiarrheal larvicidal and ovicidal activities have been reported for naturaloccurring xanthones To a certain extent this review provides necessary foundation for further research and development of newmedicines

1 Introduction

Xanthones are secondary metabolites commonly occurringin higher plant families fungi and lichen [1] Their phar-macological properties have raised great interest Structuresof xanthones are related to that of flavonoids and theirchromatographic behaviours are also similar Flavonoids arefrequently encountered in nature whereas xanthones arefound in limited number of families Xanthones always occurin the families Gentianaceae Guttiferae Moraceae Clusi-aceae and Polygalaceae Xanthones are sometimes foundas the parent polyhydroxylated compounds but most aremono- or polymethyl ethers or are found as glycosides [2]Unlike iridoids xanthones are apparently not present in allplant species investigated in the family Gentianaceae Thisis documented by the systematic work of Hostettmann etal [3] Natural occurrence of 12 xanthones in higher plantsand 4 in fungi has been reviewed by Roberts in 1961 and byDean in 1963 [4 5] Gottlieb [6] mentioned the isolation of60 xanthones from higher plants and 7 from fungi whereasCarpenter et al [7] listed 82 xanthones from higher plants

Gunasekera [8] recorded 183 xanthones from 5 families oftracheophyta According to Vieira and Kijjoa [9] out oftotal 515 xanthones 278 were reported from natural sourcesThese xanthones have been isolated from 20 families ofhigher plants (122 species in 44 genera) fungi (19 species)and lichens (3 species) In this period the xanthones fromhigher plants appear to be associatedmainly with the familiesClusiaceae (55 species in 12 genera) and Gentianaceae (28species in 8 genera) Bo and Liu [10] have reviewed separationmethods used for pharmacologically active xanthones JosePedraza-Chaverri et al [11] reviewed the isolated chemicalconstituents and medicinal properties of C Garcinia (man-gostana) Some of the plants ferns and fungus species whichcontain xanthones areArtocarpus Anthocleista AllanblackiaAndrographis Aspergillus Bersama Blackstonia Calophyl-lum Canscora Centaurium Chironia Cratoxylum Comas-toma Garcinia Cudrania Eustoma Emericella FraseraGarcinia Gentiana Gentianella Gentianopsis Halenia Hop-pea Hypericum Ixanthus Lomatogonium Mesua MorindaMacrocarpaea Mangrove fungi Orphium Peperomia Pen-tadesma Polygala Penicillium Phoma Phomopsis Rheedia



2 Classification
















5unit of the











2O (9 1) and MeOH-H

2O-AcOH


2O




3(3 17 vv) or
















COOHHO COOH

O

HO

O O

OHO

O

OHOH

OH

HO

O

HO

OH

OHHO

OHO

O

OH

OH

O

O OH





R998400998400O

OR998400

R998400= H R998400998400

= H gentisinR998400


R998400= H R998400998400

= Me isogentisin



50for 40


50values









Acknowledgments


References















































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



2 Classification
















5unit of the











2O (9 1) and MeOH-H

2O-AcOH


2O




3(3 17 vv) or
















COOHHO COOH

O

HO

O O

OHO

O

OHOH

OH

HO

O

HO

OH

OHHO

OHO

O

OH

OH

O

O OH





R998400998400O

OR998400

R998400= H R998400998400

= H gentisinR998400


R998400= H R998400998400

= Me isogentisin



50for 40


50values









Acknowledgments


References















































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




5unit of the











2O (9 1) and MeOH-H

2O-AcOH


2O




3(3 17 vv) or
















COOHHO COOH

O

HO

O O

OHO

O

OHOH

OH

HO

O

HO

OH

OHHO

OHO

O

OH

OH

O

O OH





R998400998400O

OR998400

R998400= H R998400998400

= H gentisinR998400


R998400= H R998400998400

= Me isogentisin



50for 40


50values









Acknowledgments


References















































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of











COOHHO COOH

O

HO

O O

OHO

O

OHOH

OH

HO

O

HO

OH

OHHO

OHO

O

OH

OH

O

O OH





R998400998400O

OR998400

R998400= H R998400998400

= H gentisinR998400


R998400= H R998400998400

= Me isogentisin



50for 40


50values









Acknowledgments


References















































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


COOHHO COOH

O

HO

O O

OHO

O

OHOH

OH

HO

O

HO

OH

OHHO

OHO

O

OH

OH

O

O OH





R998400998400O

OR998400

R998400= H R998400998400

= H gentisinR998400


R998400= H R998400998400

= Me isogentisin



50for 40


50values









Acknowledgments


References















































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of





Acknowledgments


References















































































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of
















































































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of













































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of











































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of










Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

Documents

Review Article Naturally Occurring Xanthones: Chemistry and ...Journal of Applied Chemistry ...O-Glycosides. MorethanxanthoneO-glycosidesare known. A few are from natural sources,