Cardullo Nunzio, Spatafora Carmela, Musso Nicolò, Barresi Vincenza, Condorelli Daniele, Tringali Corrado
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.
J Nat Prod. 2015 Nov 25;78(11):2675-83. doi: 10.1021/acs.jnatprod.5b00619. Epub 2015 Nov 5.
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.
已合成了一个与天然多酚白藜芦醇相关的聚甲氧基茋苷类小文库（20 - 25），并将它们与其苷元17 - 19一起针对Caco - 2和SH - SY5Y癌细胞进行抗增殖活性生物测定。其中六种化合物对至少一种细胞系表现出抗增殖活性。特别是，化合物17和18在两种细胞培养物中的至少一种上显示出高活性。化合物18对Caco - 2细胞的GI50值为3 μM，该值与抗癌药物5 - 氟尿嘧啶相当。密切相关的化合物19被证明无活性，其缀合物22和25显示出较弱的细胞生长抑制作用。结果表明，聚甲氧基茋及其苷类结构上的微小差异会显著影响抗增殖活性。还评估了β - 葡萄糖苷酶或β - 半乳糖苷酶对苷元17 - 19的可能水解释放。化合物20 - 25也作为潜在的β - 葡萄糖苷酶、β - 半乳糖苷酶和α - 葡萄糖苷酶抑制剂进行了测试。观察到化合物21（IC50 = 78 μM）和25（IC50 = 70 μM）对α - 葡萄糖苷酶具有有前景的抑制活性，这可能表明它们作为开发抗糖尿病或抗肥胖药物的先导化合物的潜力。
