Resveratrol-Related Polymethoxystilbene Glycosides: Synthesis, Antiproliferative Activity, and Glycosidase Inhibition

Abstract

A small library of polymethoxystilbene glycosides (20-25) related to the natural polyphenol resveratrol have been synthesized and subjected, together with their aglycones 17-19, to an antiproliferative activity bioassay toward Caco-2 and SH-SY5Y cancer cells. Six of the compounds exhibit antiproliferative activity against at least one cell line. In particular, compounds 17 and 18 proved highly active on at least one of the two cell cultures. Compound 18 showed a GI50 value of 3 μM against Caco-2 cells, a value comparable to that of the anticancer drug 5-fluorouracil. The closely related compound 19 proved inactive, and its conjugates 22 and 25 showed weak cell growth inhibition. The results indicate that minimal differences in the structure of both polymethoxystilbenes and their glycosides can substantially affect the antiproliferative activity. The possible hydrolytic release of the aglycones 17-19 by β-glucosidase or β-galactosidase was also evaluated. Compounds 20-25 were also tested as potential β-glucosidase, β-galactosidase, and α-glucosidase inhibitors. A promising inhibitory activity toward α-glucosidase was observed for 21 (IC50 = 78 μM) and 25 (IC50 = 70 μM), which might be indicative of their potential as lead compounds for development of antidiabetic or antiobesity agents.

Synthesis, Biological Evaluation and Molecular Modeling Studies of New Oxadiazole-Stilbene Hybrids against Phytopathogenic Fungi

“…Among those stilbenes, resveratrol ( Fig. 1 ) and its natural derivatives have attracted considerable interest both for their roles in plant defenses 1 2 and for their beneficial impacts on human health 3 4 5 6 7 . Much effort dedicated to the later aspects has highlighted the health-promoting properties, one of which is associated with their chemopreventive and therapeutic effects against human cancers 3 4 5 .…”

Anticancer Activity of Stilbene‐Based Derivatives

“…Phenols 14 and 15 (Figure ) are antiangiogenic agents acting on granulosa cell VEGF production . Compounds 14 and 15 also showed high antiproliferative activity toward Caco‐2 and SHSY5Y cancer cells, with a GI 50 value of 3 μ m …”

“…[62] Compounds 14 and 15 also showed high antiproliferativea ctivity toward Caco-2 and SHSY5Y cancercells, with aGI 50 value of 3 mm. [86] Glucosides andg alactosides of the active aglycones 14 and 15 lacked antiproliferativea ctivity even if glycosides display antitumora ctivity or other promising biologicalp roperties [87] and resveratroloside showed cytotoxic activity against human tumor cell lines. This fact could be due to poor hydrolysis by intracellular enzymes;they also showed b-glucosidase or b-galactosidase inhibition with IC 50 values in the range of 170-350 mm,c ompared with the antidiabetic drug acarbose (IC 50 = 65 mm).…”

Mass Spectrometry and 1H-NMR Study of Schinopsis lorentzii (Quebracho) Tannins as a Source of Hypoglycemic and Antioxidant Principles

“…Moreover, the well-known antioxidant properties of polyphenols represent a further advantage in the search for potential dual-action antidiabetic agents, able to join hypoglycemic properties and reduction in oxidative damage associated with diabetes complications [ 2 ]. Consequently, several analogues of natural polyphenols have been evaluated as hypoglycemic agents, namely stilbenoid glycosides [ 9 ], bisphenol neolignans [ 10 ], rosmarinic acid amides [ 11 ], 3,4-dihydroxypyrrolidine-based compounds [ 12 ], and biscoumarins [ 13 ].…”