Flavonoids and cinnamic acid derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase type 1

17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) type 1 converts estrone to estradiol, a potent ligand for estrogen receptors. It represents an important target for the development of drugs for treatment of estrogen-dependent diseases. In the present study, we have examined the inhibitory activities of some flavonoids, their biosynthetic precursors (cinnamic acids and coumaric acid), and their derivatives. The proliferative activity of flavonoids on the T-47D estrogen-receptor-positive breast cancer cell line was also evaluated. Among 10 flavonoids, 7,4'-dihydroxyflavone, diosmetin, chrysoeriol, scutellarein, genkwanin and fisetin showed more than 70% inhibition of 17 beta-HSD type 1 at 6 mu M. In a series of 18 derivatives of cinnamic acid, the best inhibitor was 4'-cyanophenyl 3,4-methylenedioxycinnamate, with more than 70% inhibition of 17 beta-HSD type 1. None of flavonoids affected the proliferation of T-47D breast cancer cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.