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

A small library of polymethoxystilbene glycosides (20−25) related to the natural polyphenol resveratrol have beensynthesized and subjected, together with their aglycones 17−19, to an antiproliferative activity bioassay toward Caco-2 and SHSY5Ycancer cells. Six of the compounds exhibit antiproliferative activity against at least one cell line. In particular, compounds 17and 18 proved highly active on at least one of the two cell cultures. Compound 18 showed a GI50 value of 3 μM against Caco-2cells, a value comparable to that of the anticancer drug 5-fluorouracil. The closely related compound 19 proved inactive, and itsconjugates 22 and 25 showed weak cell growth inhibition. The results indicate that minimal differences in the structure of bothpolymethoxystilbenes and their glycosides can substantially affect the antiproliferative activity. The possible hydrolytic release ofthe 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 for21 (IC50 = 78 μM) and 25 (IC50 = 70 μM), which might be indicative of their potential as lead compounds for development ofantidiabetic or antiobesity agents.