Chemo-enzymatic synthesis and cell-growth inhibition activity of resveratrol analogues.
The stilbenoid resveratrol (1) was subjected to regioselective acetylation catalysed by Candida antarctica lipase (CAL) to obtain 4'-acetylresveratrol (2). CAL biocatalysed regioselective alcoholysis of 3,5,4'-triacetylresveratrol (3), 3,5,4'-tributanoylresveratrol (6), and 3, 4, 5'-trioctanoylresveratrol (9) afforded derivatives 4, 5, 7, 8, 10, and 11. Further resveratrol analogues (12-18) were obtained through methylation and hydrogenation reactions, whereas the 3,4,4'-trimethoxystilbene (19) was obtained by complete synthesis. Resveratrol and its lipophylic analogues were subjected to cell-growth inhibition bioassays towards DU-145 human prostate cancer cells. Compounds 2-19 showed cell-growth inhibition activity comparable to or higher than resveratrol (GI(50)=24.09 microM), displaying low or very low toxicity against non-tumorigenic human fibroblast cells. Comparison of the trimethoxy stilbenes 12 (GI(50)=2.92 microM) and 19 (GI(50)=25.39 microM) indicates that the position of the substituents is important for the activity. The marked activity of methyl ethers 12, 13, and 18 in comparison with that of the corresponding esters suggests that the different chemical reactivity, rather than steric factors, strongly influences the activity.
Cardile
Venera
V
Dipartimento di Scienze Fisiologiche, Università di Catania, Viale A. Doria 6, 95125 Catania, Italy.
Lombardo
Laura
L
Spatafora
Carmela
C
Tringali
Corrado
C
D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002175:Candida / Q000201:enzymology; D002384:Catalysis; D002455:Cell Division / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006865:Hydrogenation; D008049:Lipase / Q000378:metabolism; D008297:Male; D008745:Methylation; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D013267:Stilbenes; D008049:Lipase; D000077185:Resveratrol