1 Journal of Applied Pharmaceutical Research 2015, 3(4): 01-07 JOURNAL OF APPLIED PHARMACEUTICAL RESEARCH ISSN No. 2348 – 0335 www.japtronline.com STILBENES: CHEMISTRY AND PHARMACOLOGICAL PROPERTIES Chetana Roat*, Meenu Saraf Department of Microbiology & Biotechnology, University School of Sciences, Gujarat University, Ahmedabad, Gujarat 380009, India Article Information ABSTRACT: Medicinal plants are the most important source of life saving drugs for the Received: 21st September 2015 majority of the Worlds’ population. The compounds which synthesized in the plant from the Revised: 15th October 2015 secondary metabolisms are called secondary metabolites; exhibit a wide array of biological and Accepted: 29th October 2015 pharmacological properties. Stilbenes a small class of polyphenols, have recently gained the focus of a number of studies in medicine, chemistry as well as have emerged as promising Keywords molecules that potentially affect human health. Stilbenes are relatively simple compounds Stilbene; Chemistry; synthesized by plants and deriving from the phenyalanine/ polymalonate route, the last and key Structures; Biosynthesis pathway; enzyme of this pathway being stilbene synthase. Here, we review the biological significance of Pharmacological properties stilbenes in plants together with their biosynthesis pathway, its chemistry and its pharmacological significances. INTRODUCTION quantities are present in white and rosé wines, i.e. about a tenth Plants are source of several drugs of natural origin and hence of those of red wines. Among these phenolic compounds, are termed as the medicinal plants. These drugs are various trans-resveratrol, belonging to the stilbene family, is a major types of secondary metabolites produced by plants; several of active ingredient which can prevent or slow the progression of them are very important drugs. Essentially, plant cell produced the major diseases, as well as extend the lifespans of various two types of metabolites: primary metabolites involved directly organisms from yeast to vertebrates [2,3]. Other natural stilbenes in growth and metabolism, viz., carbohydrates, lipid and derived from resveratrol such as pterostilbene or piceatannol, protein, and secondary metabolites considered as the end display higher oral bioavailability and bioactivity than the product of primary metabolism and in general not involved in parent compound, but are far less abundant in natural sources[4]. metabolic activity, viz., alkaloids, phenolics, essential oils, Some t-resveratrol analogues such as polyhydroxy and steroids, lignins, tannins etc. The plant biomasses cultivated in polymethoxy derivatives exhibit higher pharmacological vitro are capable of biosynthesis of secondary metabolites activity than the parent compound [5]. typical for intact plants or they may serve as sources of entirely new molecules, not identified in nature. In effect, a path was Epidemiology opened for intensive biotechnological research into the Some epidemiologic studies in United States have examined potential use of in vitro cultures to produce highly valuable the relationship between wine consumption and the risk of secondary metabolites, including compounds for which cancer. Contrary to other alcoholic beverages, the moderate medical application could be found[1] . Polyphenolics are wine consumption was associated with a decrease (or no important constituents of grapes in determining the colour, increase) in the risk of oral and pharyngeal cancer [6] and breast taste and body of wines. Unlike other alcoholic beverages, red cancer[7] using small cohorts in Italy found a minimum risk of wine, which is obtained after maceration, contains phenolic cancer and cardiovascular disease associated with moderate compounds in high concentration up to 4 g/l, but relatively low alcohol consumption (wine being the main beverage). *For Correspondence: [email protected]; Contact No: +91 79 2630 3225; Fax: +91 79 26303225 ©2015 The authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY NC), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers. Roat et. al Stilbenes: chemistry and pharmacological properties Chemistry different chemical characteristics and biological activities. The Stilbenes naturally occur in several plant families, such as the trans-isomer is usually the more stable, and cis-trans- Cyperaceae, Dipterocarpaceae, Gnetaceae, and Vitaceae[8]. interconversions can occur in the presence of heat or ultraviolet Grapes (Vitaceae) and products manufactured from grapes are light.Other simple stilbenes have been isolated in Vitis viewed as the most important dietary sources of these vinifera : trans-pterostilbene and piceatannol. Besides the substances[9] .They are a family of molecules belonging to the aglycone of resveratrol cited above, some resveratrol non-flavonoid polyphenol group. The essential structural glucosides derivatives have been identified such as piceid and skeleton comprises two aromatic rings joined by an ethylene resveratroloside, two β-glucosides of resveratrol [10] together bridge (C6-C2-C6).From this relatively simple structure, there is with astringin (piceatannol 3-O-β-glucoside). These a large array of compounds: - monomers which varying in the compounds exist in their two isomeric forms, cis and trans number and position of hydroxyl groups, the substitution with (Waffo-Téguo et al., 1998). Furthermore, resveratrol di- and sugars, methyl, methoxy and other residues and the steric tri- glucoside derivatives have been recently isolated from Vitis configuration of the molecules (Fig. 1), - oligomers resulting vinifera [11.12]. from the different oxidative condensation of resveratrol monomer (dimers, trimers, tetramers,……). Oligomers R 4 R1 Besides monomers of stilbenes, some oligomers have been 3' R3 isolated from Vitis vinifera. They are eithers dimers, trimers 4' 7 1' and tetramers. These oligomers result from the different R1 3 1 8 R2 oxidative condensation of resveratrol monomer. R4 trans cis 5 R3 Dimmers R2 Figure 1: Structure of the main stilbene monomer derivatives The dimers are divided into two major groups. One group (A) from Vitis vinifera contains one five-membered oxygen heterocyclic ring bearing to aromatic ring (benzofuran ring) (Fig 2). Belonging this group, we have α-viniferin substituted or not with sugars[13] , α- names R1 R2 R3 R4 viniferin (also named resveratrol dehydrodimer) glucosylated cis- and trans-resveratrol OH OH 0H H or not[14] (Waffo et al., 2001) and α-viniferifuran[15] (Fig 2).The trans-pterostilbene OCH3 OCH3 OH H other group (group B) does not contain any oxygen cis- and trans-piceid OGlc OH OH H heterocyclic ring. Among dimers belonging to this group, cis- and trans- OH OH OGlc H pallidol have been isolated in Vitis vinifera as well as its mono- resveratroloside and di-glucoside [14, 13] and parthenocissin A (Fig 3). cis- and trans-resveratrol OGlc OGlc OH H 2.2.4 – Trimers 3,5-O-β-diglucoside Recently, resveratrol trimer was detected in grapevine infected cis- and trans-resveratrol OGlc OH OGlc H by downy mildew using HPLC coupled to Atmospheric 3,4’-O-β-diglucoside Pressure Photoionisation (APPI) mass spectrometry. The trans-resveratrol 3,5,4’- OGlc OGlc OGlc H structure was supposed to be α-viniferin [15] (Fig.4). O-β-triglucoside 2.2.5 – Tetramers trans-piceatannol OH OH OH OH Besides resveratrol dimers and trimer, stilbene tetramers were cis- and trans-astringin OGlc OH OH OH isolated from Vitis vinifera. They are divided into three groups: one group contains a bicyclo[6.3.0]undecane ring system. Into Monomers (Fig 1) this group we have viniferol A (Fig. 5). Second group has a Among stilbene monomers, resveratrol (3, 5, 4’- bicyclo[5.3.0]decane ring system. Resveratrol tetramers trihydroxystilbene) has been identified as the major biological belonging to this group are: viniferal B and C, vaticanol B, and active compound, and most of the studies have focused on it. vaticaphenol A (Fig.5) third group contains benzofuran system The two isomeric forms of resveratrol (cis- and trans-) have usually trans-2-aryl-2,3-benzofuran moiety (Fig 6). Tetramers Journal of Applied Pharmaceutical Research October – December 2015 Volume 3 Issue 4 2 Roat et. al Stilbenes: chemistry and pharmacological properties HO belonging this group are: vitisifuran A and B and iso- and HO [14] 7 O OH hopeaphenol (two cyclic symmetric tetramers) (Ito et al., 7 O OH HO 8 OH 1997). HO 8 OH HO OH 4 OH OH OH O 7 O OH 11 ' OH HO 1 OH HO O O 8 9 O R1 HO OH 9' OH 8' 11 OH R1 7' 13 OH HO HO O 1' R2 OH OH OH ci s R2 trans-ε-viniferifuran tr a n s vitisifuran A vitisifuran B 4' vitisin A, H-7 and H-8 =dihydro vitisin B H-7 and H-8 =dihydro OH OH R 1 = R 2 = O H , t r a n s - ε- v i ni f e r in R 1 = R 2 = O Gl c , c i s - a n d t ra n s -ε - vi n i fe r i n 1 1 , 1 3 - O -β - d i g l u co s i d e HO HO OH OH 4 OH O OH O OH 4' O 7 1 HO OH HO 8 9 OH H H 7' 1' R1 11 H H OH OH 9' 8' 13 11 ' OH OH R2 OH HO O HO O OH OH OH R1 =R2 =OH, trans-δ- viniferin OH OH hopeaphenol isohopeaphenol R 1 =O G l c ,R 2 = O H , tr a n s - δ- v in i f er i n 11 - O - β-glucoside R 1 = O H , R 2 = O Gl c , t r an s -δ - v i n i f e r i n 1 1 ' - O -β-glucoside Figure 2: Structure of the main stilbene dimer derivatives Figure 6: Structure of the stilbene tetramer from Vitis vinifera (group A) from Vitis vinifera Shikimate phenylalanine