Anticancer activity of 3-O-acyl and alkyl-(−)-epicatechin derivatives

We report the synthesis and anticancer effects of 3-O-acyl and alkyl-(−)-epicatechin derivatives. By changing the structure or replacing the gallate group of (−)-ECG, 3-O-acyl and alkyl-(−)-epicatechin derivatives were synthesized to be screen as anticancer agents using the MTT assay in vitro against cancer cell lines (PC3, SKOV3, U373MG). 3-O-Acyl and alkyl-(−)-epicatechin derivatives (4–25) exhibited better anticancer activity than (−)-ECG and specially, compounds 6–8, 17–19, which were modified aliphatic chains with moderate sizes (C8–C12) showed strong anticancer activity (IC50=6.4–31.2μM). The introduction of an alkyloxy group on 3-O-hydroxyl instead of an acyloxy group significantly enhanced inhibitory activity. Consequently, the compound that showed the most potency as anticancer agents were 3-O-decyl-(−)-epicatechin (18) (IC50=8.9, 7.9, 6.4μM against PC3, SKOV3, U373MG, respectively), which modified the appropriate lipophilic group on the C-3 hydroxyl as an alkyloxy group.