Flavonoids and cinnamic acid derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 1.
17beta-Hydroxysteroid dehydrogenase (17beta-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 17beta-HSD type 1 at 6microM. In a series of 18 derivatives of cinnamic acid, the best inhibitor was 4'-cyanophenyl 3,4-methylenedioxycinnamate, with more than 70% inhibition of 17beta-HSD type 1. None of flavonoids affected the proliferation of T-47D breast cancer cells.
Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Petra
P
Brozic
Petra
P
Kocbek
Matej
M
Sova
Julijana
J
Kristl
Stefan
S
Martens
Jerzy
J
Adamski
Stanislav
S
Gobec
Tea
T
Lanisnik Rizner
D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004960:Estradiol Dehydrogenases / Q000037:antagonists & inhibitors*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular
D002934:Cinnamates; D004791:Enzyme Inhibitors; D005419:Flavonoids; C029010:cinnamic acid; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human