Anti-tumor Properties of Stilbene-based Resveratrol Analogues: Recent Results:

Recent literature about stilbene-based analogues of resveratrol (1) has been reviewed, and a total of 94 compounds are reported (see structures 4 – 97), selected either for their promising anti-tumor properties or as comparative terms in SAR studies. As a general outline, these recent literature data confirm the previously reported observation that minimal modification in the nature and position of the substituents on the stilbene nucleus may cause large variations in their biological activity and, more specifically, in their anti-tumor properties. Among the polyhydroxylated stilbenes, it has been established that those with either a catechol or pyrogallol moiety are far better radical scavengers than either 1 or other analogues lacking an ortho-dihydroxy group, and this property was shown to be related to pro-apoptotic activity. In the large majority of cases where couples of E- and Z-isomers were evaluated for either cytotoxic or pro-apoptotic activity, the Z-isomers were significantly more active than their E analogues; nevertheless, a general rule stating that stilbenoids with Z configuration of the double bond display a considerably higher antiproliferative activity than their E-isomers cannot be considered as established. A variety of methoxystilbenes has been reported recently: in many cases these analogues showed either potent antiproliferative and pro-apoptotic activity or strong inhibition of TNFα-induced activation of NF- kB. Globally considered, polymethoxystilbenes are a sub-group of great interest among the resveratrol analogues: these analogues appear worthy of a deeper evaluation also in connection with their potential anti-angiogenic properties. In addition, in vivo studies indicate that methoxystilbenes undergo different metabolic conversion and have a higher bioavailability than resveratrol. The potent activity of some amino- and halogenated stilbenes is undoubtedly worthy of attention, but the toxicity of these compounds to normal cells has rarely been evaluated. In conclusion, the synthesis and evaluation of stilbene-based resveratrol analogues proved to be a highly active field of research and has recently afforded compounds with either cytotoxic or pro-apoptotic activity in the nanomolar range. Nevertheless, the exact structural determinants to optimize the anti-tumor properties of these compounds and details of their mechanism of action remain to be clarified

Antiangiogenic resveratrol analogues by mild m-CPBA aromatic hydroxylation of 3,5-dimethoxystilbenes.

A mild treatment of the resveratrol analogue 3,5,4′-trimethoxystilbene 2 with m-CPBA afforded two hydroxylated methoxystilbenes 5 and 6 by direct aromatic hydroxylation. A similar protocol was applied to other stilbenes bearing a 3,5-dimethoxy moiety, namely tetramethoxystilbenes 7 and 10 to obtain respectively the hydroxylated analogues 8, 9 and 11, 12. The substrate 2 and the new compounds 5, 8 and 11 were evaluated as anti-angiogenic agents and proved significantly active in the range 1 – 100 μM

Bioassay-guided isolation of antiproliferative compounds from grape (Vitis vinifera) stems.

The fractionation, guided by cell-growth inhibition assay, of the EtOAc crude extract from grape stems of the Sicilian Vitis vinifera variety 'Nerello Mascalese' allowed identification of ten constituents, isolated either as pure compounds (1, 3–5, 7–10) or inseparable mixtures (2a-d and 6a-e). The pure constituents were: two triterpenoid acids, oleanolic (1) and betulinic acids (5); daucosterol (7); a stilbenoid, E-resveratrol (3) and its dimer E-ε-viniferin (4); the simple phenol gallic acid (8); and the flavanols catechin (9) and gallocatechin (10). Four 6′- O-acyldaucosterols (2a-d) and five 1,2-di- O-acyl-3- O-β-D-galactopyranosyl glycerols (6a-e) were also identified as inseparable mixtures. All the isolated compounds were subjected to spectroscopic analysis and MTT bioassay on MCF-7 human breast cancer cells. The majority showed growth-inhibitory activity, 5 being the most active (GI50 = 0.57 μM). Compounds 3–5 were also tested on HT-29, U-87-MG and U-373-MG cell lines

Interaction of resveratrol analogues with biomembrane models: a calorimetric study on structural variations effects

Differential Scanning Calorimetry was used to study the interaction of new resveratrol derivatives using dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV) as biomembrane models. MLV prepared in the presence of increasing molar fractions of the following compounds: (A) 3,5,3’,5’- tetramethoxystilbene, (B) 3,5,3’,4’-tetramethoxystilbene, (C) 3,4,5,4’-tetramethoxystilbene, (D) 3,4,5,3’,5’- pentamethoxystilbene and (E) 3,4,2’,4’,5’-pentamethoxystilbene were analyzed to study the effects exerted by the number and position of the substituents on the variations of thermotropic properties of the biomembrane model. The results showed that the number and the position of the substituent strongly affected the interaction between the compounds and the MLV based on DMPC. Kinetic experiments demonstrated that, the absorption of compounds A to E is limited in an aqueous medium. The presence of a lipophilic medium improves the absorption of the compounds by the biomembrane model

Valorization of Agri-Food Waste from Pistachio Hard Shells: Extraction of Polyphenols as Natural Antioxidants

The agricultural processing industry usually generates a remarkable amount of by-products rich in bioactive compounds, which can be exploited for agri-food or nutraceutical applications. Pistachio’s hard shell is one of the major by-products from pistachio industrial processing. The aim of this work was the evaluation of pistachio shells as a potential source of natural antioxidants. We evaluated different extraction procedures by measuring total phenolic content, total flavonoid content and antioxidative activity (DPPH•, TEAC and ORAC). The microwave-assisted ethanol extract turned out to be the most promising and was fractionated by XAD-16 column chromatography, affording six fractions analyzed through HPLC/ESI-MS/MS and 1H-NMR to identify the main antioxidative constituents. Fractions Fr4–Fr6 demonstrated the highest antioxidant activity. Gallic acid and a monogalloylglusose isomer are the main phenolic constituents of Fr4. Both simple and complex phenolics, such as flavonoids and hydrolysable tannins, were identified in fractions Fr5 and Fr6; pentagalloylglucose and kaempferol, well-known for their antioxidant activity, are the most abundant constituents. The results highlighted that the proposed methodology can be an effective way to recover bioactive phenolic compounds from pistachio hard shell, making this by-product a promising source of compounds with potential applications in food and healthcare sectors

Reaction of benzoxanthene lignans with peroxyl radicals in polar and non-polar media: cooperative behaviour of OH groups

Benzo[kl]xanthene lignans, promising bioactive polyphenols obtained by biomimetic oxidative coupling of caffeic acid derivatives, react efficiently with peroxyl radicals in both polar and non polar solvents, thanks to the simultaneous presence of guaiacol like and catechol-like OH-groups