title: 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.
authors.affiliation: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Bio-Mediche, Sezione di Biochimica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Cardullo
authors.affiliation: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Bio-Mediche, Sezione di Biochimica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Spatafora
authors.affiliation: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Bio-Mediche, Sezione di Biochimica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Musso
authors.affiliation: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Bio-Mediche, Sezione di Biochimica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Barresi
authors.affiliation: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Bio-Mediche, Sezione di Biochimica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Condorelli
authors.affiliation: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Bio-Mediche, Sezione di Biochimica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Tringali
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D065089:Glycoside Hydrolase Inhibitors; D006027:Glycosides; D013267:Stilbenes; D000520:alpha-Glucosidases; D000077185:Resveratrol; D005472:Fluorouracil