Stilbene Oligomers Research Articles

Photo-switchable field-effect transistors based on two-dimensional stilbene oligomer crystals

Large-size two-dimensional photochromic semiconductor single crystals of stilbene oligomers are prepared for application in photo-switchable organic field-effect transistors.

13C NMR and LC-MS Profiling of Stilbenes from Elicited Grapevine Hairy Root Cultures.

Resveratrol and related oligostilbenes are defense molecules produced by grapevine in response to stresses including various elicitors or signal molecules. Together with their prominent role in planta, these compounds have been the center of much attention in recent decades due to their pharmacological properties. The cost-effective production of resveratrol derivatives such as viniferins or more structurally complex stilbene oligomers remains a challenging task. In this study, the chemical diversity of stilbenes produced by Vitis vinifera Pinot Noir hairy roots was investigated after elicitation for 4 days with a mixture of methyl jasmonate (100 μM) and cyclodextrins (50 mM). Two crude extracts obtained from the culture medium and from the hairy roots were fractionated by centrifugal partition chromatography. The fractions were chemically investigated by two complementary identification approaches involving a 13C NMR-based dereplication method and liquid chromatography coupled to mass spectrometry (LC-MS). In total, groups of 21 and 18 molecules, including flavonoids and stilbenes, were detected in the culture medium and root extracts, respectively. These included resveratrol monomers, dimers, trimers, and a tetramer, thus highlighting the ability of elicited hairy root culture systems to synthesize a wide diversity of secondary metabolites of pharmaceutical significance. The main compounds were unambiguously identified as trans-resveratrol, ε-viniferin, trans-piceatannol, pallidol, scirpusin A, eriodictyol, naringenin, vitisin B, and maackin.

Stilbene oligomer phytoalexins in grape as a response to Aspergillus carbonarius infection

Stilbenes are grapevine phytoalexins elicited by biotic and abiotic agents; Aspergillus carbonarius is a widespread ochratoxin A producing fungus present in warm conditions, such as in Southern Italy. To increase the knowledge on biosynthesis of stilbene oligomers induced by A. carbonarius infection, grape berries of the Southern Italian grape cv. Negro Amaro were inoculated. Significant increase of trans-resveratrol and resveratrol dimers and oligomers, such as caraphenol, E-ε-viniferin, ω-viniferin, δ-viniferin, α-viniferin, E-miyabenol C, and two tetramers, was observed, and concomitant decrease of glycoside derivatives. These findings improve the knowledge on the phytoalexin production as response against this pathogen.

Mass Fragmentation Patterns as Fingerprints for Positive Identification of Polyphenolic Compounds in a Crude Extract

Sixteen compounds of Neobalanocarpus heimii were successfully identified directly from their plant extract using a triple quadrupole LC-MS/MS system. In order to fulfil the objectives of this work, a series of stilbene oligomers of various degrees of condensation were isolated and their structure are characterized. Out of these, four are resveratrol dimers, three trimers, and nine tetramers. The isolation process was done on a fully automated semi-preparative HPLC system. Their structures were elucidated on the basis of 1D- and 2D-NMR as well as MS data. The mass fragmentation patterns of the compounds were recorded and a retrievable in-house library was built to keep the data. In order to demonstrate the potential of this approach, the polyphenolic crude extract was analysed with the LC-MS/MS system and the MS/MS spectra extracted for each chromatographic peak of interest. The fragmentation patterns were compared with those of anticipated pure compounds that were previously recorded. All compounds were successfully identified. It is therefore believed that the LC-MS/MS potential for dereplication of structurally similar compounds in a crude mixture was thus firmly established.

Stilbene oligomers from Carex otaruensis and Carex lanceolata

The genus Carex belongs to the family Cyperaceae and consists of approximately 1500 species distributed throughout the world. Few stilbene oligomers have been reported from this family. These oligomers are of interest due to the inconsistent isomers that result from the resveratrol framework. Herein, we explored chemical constituents within plants in the genus Carex, and report the isolation and the structural elucidation of compounds that have previously not been reported from C. otaruensis and C. lanceolata. We report the isolation of a new tetrameric stilbene (1) along with 11 known compounds. Their structures were elucidated through spectroscopic methods, including NMR experiments and MS spectra analyses.

Photo-switching effect in stilbene organic field effect transistors

In this paper, we have investigated experimentally the photo-response of the organic field effect transistors (OFETs) based on π-conjugated stilbene oligomers with mutual optical and electrical properties. The cis-trans photoisomerization of these oligomers in the active layer of the OFETs disturbs the intermolecular interactions. This perturbation disrupts the charge transport in the conduction channel and turns-off the transistor. We used this phenomenon to modulate the drain current of the OFETs optically. The photo-response activity of the transistors is temperature dependent, in agreement with the isomerization of the stilbenes. Photoluminescent evaluations verify the isomerization of the oligomers in the thin film.

Resveratrol oligomers for the prevention and treatment of cancers.

Resveratrol (3,4′,5-trihydroxystilbene) is a naturally derived phytoalexin stilbene isolated from grapes and other plants, playing an important role in human health and is well known for its extensive bioactivities, such as antioxidation, anti-inflammatory, anticancer. In addition to resveratrol, scientists also pay attention to resveratrol oligomers, derivatives of resveratrol, which are characterized by the polymerization of two to eight, or even more resveratrol units, and are the largest group of oligomeric stilbenes. Resveratrol oligomers have multiple beneficial properties, of which some are superior in activity, stability, and selectivity compared with resveratrol. The complicated structures and diverse biological activities are of significant interest for drug research and development and may provide promising prospects as cancer preventive and therapeutical agents. This review presents an overview on preventive or anticancer properties of resveratrol oligomers.

Isolation of Stilbenes from the Stem of Gnetum Microcarpum

Over the last 15 years, plant stilbenes have received considerable interest, due to their biological activities and possible pharmacological applications. Large numbers of natural stilbenes isolated from plants are oligomers which include dimers, trimers and tetramers. Gnetaceae is a family of the most advanced members of tropical gymnosperms in the order Gnetales (division Gnetophyta). It composed of only one genus, Gnetum and there are about 30 to 40 species in the tropical lowlands of the world, from northeastern South America, tropical West Africa, and south China to Southeast Asia. Various species in the family have been used as folk medicine for the treatment of arthritis, bronchitis and asthma. The leaves and the fruits are also used as food in many parts of the tropics. The plants of Gnetaceae are known to contain stilbene oligomers as their major chemical constituents, in which their structural formations are unique. In this research, the lianas of Gnetum microcarpum has been investigated. Gnetum microcarpum Blume grows in Malaysia and is not recorded in folk medicines. The standard procedures of extraction, fractionation, isolation and elucidation were used for the accomplishment of this research. The stem of Gnetum microcarpum was chopped, air dried, grind into powder and extracted using acetone. The crude extract obtained was fractioned with vacuum liquid chromatography (VLC) and each fractions were subjected to multiple column and radial chromatography techniques for isolation and purification process. Four known stilbenes were successfully isolated from the stem of Gnetum microcapum namely resveratrol (1), gnetol (2), gnetucleistol C (3) and gnetucleistol D (4). The structure of these stilbenes were determined using several spectroscopic methods which were 1D and 2D NMR, UV, IR and MS.

Occurrence of stilbene oligomers in Cyperus rhizomes

Investigation of the chemical constituents of Rhizoma Cyperi (Cyperus rotundus Linneus) resulted in the isolation of novel enantiomeric and meso-stilbene trimers [i.e., (+)- and (−)-(E)-cyperusphenol A (1, 2 respectively) and (E)-mesocyperusphenol A (3)], a trimer bearing a novel hexacyclic ring system [cyperusphenol B (5)], as well as known stilbenoids (cyperusphenols C (4) and D (6), scirpusins A (7) and B (8), and piceid (9)) and luteolin. HPLC was used for the optical resolution of 1 and 2 as well as for the identification of cooccurrence of enantiomers of 7. The structures of the isolates were established by spectroscopic analyses, including a detailed NMR spectroscopic investigation. The isolates were evaluated in terms of their antiproliferative activity employing the Jurkat cell line (human T-cell leukemia cells), while the IC50 potencies of a racemate of 1 and 2, 3, 5, and 6 were estimated as 27.4, 40.5, 26.4, and 26.3μM, respectively. The suppression of cell growth by 6 was due to the induction of apoptosis, which was characterized by nuclear changes and PARP-1 cleavage determined by western blotting. We also evaluated the free radical scavenging activity of the isolates.

Strategies and Methods for the Syntheses of Natural Oligomeric Stilbenoids and Analogues

This review covers synthetic work carried out in the field of stilbene and oligostilbene chemistry. It includes a brief overview of the methods used for the synthesis of monomeric stilbenoids. The production of oligomeric species by means of enzymatic or microbial conversion is examined in detail. Biomimetic syntheses of stilbene oligomers are then scrutinised. Most of the work is based on the dimerisation of stilbenoid monomers with help of one-electron oxidants or through acid catalysis. Mechanistic interpretations of the oxidative couplings observed by the various groups are proposed and suggest that the outcome of these reaction be guided by the “hard and soft acid and base” (HSAB) principle together with supramolecular interactions between the reacting stilbenoid monomers. Eventually, the few non-biomimetic full syntheses are presented and their strategies analysed. Keywords: Stilbene, Oligostilbene, Biomimetic synthesis, One-electron oxidants, Enantioselective synthesis

Novel isolation of stilbenoids with enantiomeric and meso forms from a cyperus rhizome

Three stereoisomeric stilbene trimers bearing an (E)-2,3,5,6-tetraphenyl-4-styryl-2,3,5,6-tetrahydrobenzo[1,2-b:5,4-b′]difuran skeleton, (+)- and (−)-(E)-cyperusphenol A (1, 2) and (E)-mesocyperusphenol A (3), were isolated from a cyperus rhizome. Moreover, the geometrical isomers (4–6) were identified as the artifacts of their (E)-forms (1–3). The isolated products are the first instance of the co-occurrence of racemates (1, 2: new compounds) and a meso isomer (3), which resembles the C2 symmetrical structure of an oligostilbenoid. These structures were characterized by NMR and CD spectroscopy. This is the first report that shows the occurrence of a racemate of a stilbenoid in the same plant material and the achievement of the optical separation of stilbene oligomers.

Dimerization of piceatannol by Momordicacharantia peroxidase and α-glucosidase inhibitory activity of the biotransformation products

Stilbenes, especially those oligomers, have great potential to be antihyperglycemic agents. In this study, eight stilbene dimers, including five new ones, were obtained by biotransformation of piceatannol using Momordicacharantia peroxidase (MCP) for the first time. Their structures were established on the basis of spectroscopic evidences. These piceatannol dimers displayed potential α-glucosidase inhibitory activities, and trans double bond, tetrahydrofuran ring, and free adjacent phenolic dihydroxyls were found to be important for their activities. Enzymatic biotransformation of stilbenes by M.charantia peroxidase (MCP) was showed to be a prominent way to produce oligomeric stilbenes for antihyperglycemic development.

Neuroprotective effect of parthenocissin A, a natural antioxidant and free radical scavenger, in focal cerebral ischemia of rats

Neuroprotective effects of parthenocissin A (PA), a novel antioxidant and free radical scavenger, were studied in a transient middle cerebral artery (MCA) occlusion model in rats for the first time. The animals were treated intraperitoneally with PA at 2.5, 5 or 10 mg/kg, for both 30 min before MCA occlusion and 6 h after reperfusion. The MCA was occluded for 1 h in anesthetized Sprague-Dawley rats. Compared with vehicle-treated controls, MCA occluded animals treated with PA showed dose-dependent reductions in brain infarction size with improved neurological and motor outcome. Biomedical assay showed that the PA treatment suppressed lipid peroxidation and restored superoxide dismutase (SOD) activity in brain tissue. In addition, the ischemia/reperfusion (I/R) induced elevation of nitric oxide (NO) production and nitric oxide synthase (NOS) activity in brain tissue was also inhibited. Thus, PA demonstrated a neuroprotective effect in the I/R model and the beneficial effects of the compound may result from the reduction of oxidative stress and the inhibition of NO production induced by I/R. The neuroprotective effects of PA have highlighted the potential use of stilbene oligomers in stroke therapy.

α-Glucosidase Inhibitiors from Seed Extract of Paeonia lactiflora

Alpha-glucosidase inhibitors are oral antihyperglycemic agents that act on alpha-glucosidase competitively, delaying intestinal carbohydrate absorption and lessening postprandial increases in glucose levels. In the search for new classes of α-glucosidase inhibitors extracted from natural resources, 420 different plant extracts were evaluated for their inhibitory effect on α-glucosidase, in vitro. Amongst the tested extracts, the seed extract of Paeonia lactiflora (Paeoniaceae) demonstrated a significant degree of inhibition on the enzyme, according to dose. Extensive bioassay-guided fractionation of the extract resulted in the isolation of six materials, luteolin (1), resveratrol (2), trans-e-viniferin (e), gnetin H (4), suffruticosol A (5) and suffruticosol B (6), that are active agents for α-glucosidase inhibition. Resveratrol (2) is a well-known naturally occurring hydroxystilbene, particularly abundant in wine and some related stilbene oligomers. Materials (3-6) exhibited relatively strong inhibition of α-glucosidase and their IC50 values were calculated as: 0.92mM (2), 3.15mM (3), 1.15 mM (4), 2.53mM (5) and 3.15mM (6). In contrast, the (IC50) value of the reference drug, acarbose, was estimated as 8.28mM in vitro.

Preparative isolation and purification of antioxidative stilbene oligomers from Vitis chunganeniss using high‐speed counter‐current chromatography in stepwise elution mode

Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of three stilbene oligomers from Vitis chunganeniss using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (2:5:2:5, v/v) and (1:2:1:2, v/v). The preparative HSCCC separation was performed on 800 mg of crude sample yielding hopeaphenol (21.1 mg), amurensin G (37.2 mg) and vitisin A (95.6 mg) in a one-step separation, with purities over 95% as determined by HPLC. The structures of these three compounds were identified by MS, (1)H NMR and (13)C NMR. In addition, their antioxidant activities were screened by DPPH assay, where vitisin A showed strong antioxidant activity. Further EPR experiments with spin-trapping technique demonstrated that vitisin A is a potent and selective singlet oxygen quencher, which may be used in singlet oxygen-mediated diseases as a pharmacological agent.

Purification of novel stilbene oligomers from vine stalks by centrifugal partition chromatography guided by mass spectrometry

Stilbenes are known to be frequently encountered in a limited number of families: Cyperaceae, Dipterocarpaceae, Gnetaceae, and Vitaceae [1]. Resveratrol (E-3,5,4'-trihydroxystilbene), a naturally occurring phenolic compound, has been spotlighted as a potential chemopreventing agent for several pathologies such as cardiovascular and neurodegenerative diseases and different types of cancer [2]. Wine and grapes are the principal dietary sources of these compounds. In order to dispose important quantities of various stilbenes to test their biological activities in vitro and in vivo, a purification of oligostilbenes guided by mass spectrometry was undergone on Vitis vinifera cv merlot stalk extracts using centrifugal partition chromatography (CPC). In this study, the quaternary Arizona solvent systems (n-heptane/EtOAc/MeOH/Water) [3] were successfully used for the isolation of an hexamer and three trimers of resveratrol from stalks of Vitis vinifera, along with a multitude of other stilbenic compounds.

Stilbene Oligomers from Parthenocissus laetevirens: Isolation, Biomimetic Synthesis, Absolute Configuration, and Implication of Antioxidative Defense System in the Plant

Five new stilbene oligomers, laetevirenol A-E (4-8), were isolated from Parthenocissus laetevirens, together with three known stilbene oligomers (2, 3, and 9). The structures of the new compounds were elucidated by spectroscopic analysis, including 1D and 2D NMR experiments. Afterward the absolute configurations were determined. Biomimetic transformations revealed a possible biogenetic route, where stilbene trimers were enzymatically synthesized for the first time. In addition, their antioxidant activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The results showed that stilbene oligomers with an unusual phenanthrene moiety exhibited much stronger antioxidant activities. Thus, the photocatalyzed cyclization of stilbenes was supposed to be an antioxidant activity promoting transformation, which was hypothesized to play a role in the antioxidative defense system of the plant.

Antibacterial Activity of Stilbene Oligomers against Vancomycin-Resistant Enterococci (VRE) and Methicillin-Resistant Staphylococcus aureus (MRSA) and Their Synergism with Antibiotics

Two resveratrol trimers, gnemonol B isolated from Gnetum gnemon and gnetin E obtained from the Gnetum species, were found to exhibit strong antibacterial activities against vancomycin-resistant Enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). The MIC values of gnemonol B against five strains of VRE and nine strains of MRSA were 12.5 and 6.25 microg/ml, respectively. The MIC values of gnetin E against five strains of VRE and nine strains of MRSA ranged from 12.5 to 25microg/ml. These compounds also showed synergistic effects when used in combination with commercially available antibiotics according to the evaluation method using FIC indices. These findings suggested that the application of the test compounds alone or in combination with antibiotics might be useful in controlling and treating VRE and MRSA infections

Inhibitory Activity of Plant Stilbene Oligomers against DNA Topoisomerase II

The inhibitory activity of 40 stilbene oligomers isolated from six plant species against topoisomerase II was evaluated, of which nine compounds showed a potent inhibitory effect, stronger than daunorubicin, a topoisomerase II inhibitor, used as an anti-cancer drug. The specificity of active stilbene oligomers on topoisomerase II was assessed by their effect on DNA restriction enzyme. In particular, specific inhibitory activity was observed in alpha-viniferin 13-O-beta-glucopryranoside (2) and hemsleyanol C (13).

Simultaneous Determination of the Contents of Three Stilbene Oligomers in Caragana sinica Collected in Different Seasons Using an Improved HPLC Method

The objectives of this research were to determine simultaneously the contents of two stilbene tetramers, carasinol B (1) and kobophenol A (2), and one stilbene trimer, (+)-alpha-viniferin (3), in the roots, tubers, and leaves of Caragana sinica in various seasons. A HPLC method has been developed for efficiently quantifying the three analytes in the plant. Using this method, different samples of Caragana sinica were evaluated. The results showed that the contents of 1, 2, and 3 in the roots were much higher than those in the tubers, and the contents of stilbene tetramers were maximal in winter while the contents of the stilbene trimer were maximal in summer. Compounds 1, 2, and 3 could not be detected in the flowers of Caragana sinica in our detection ranges.