Chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities.
Chalcones were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. In the present study, we have demonstrated for the first time that chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities: these enzymes being considered as important targets in the metabolic pathways of human mammary hormone-dependent cells. Our results showed that naringenin chalcone and 4-hydroxychalcone were the most effective aromatase and 17beta-hydroxysteroid dehydrogenase inhibitors with IC50 values of 2.6 and 16 microM respectively. In addition, inhibitory effects of some flavones and flavanones were compared to those of the corresponding chalcones. A structure-activity relationship was established and regions or/and substituents essential for these inhibitory activities were determined.
Le Bail
J C
JC
UPRES EA 1085, Biomolecules et cibles cellulaires tumorales-Prolifération cellulaire et inhibition enzymatique Laboratoire de Biochimie, Faculté de Pharmacie, Limoges, France.
Pouget
C
C
Fagnere
C
C
Basly
J P
JP
Chulia
A J
AJ
Habrioux
G
G
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000735:Androstenedione / Q000378:metabolism; D047072:Aromatase Inhibitors; D002599:Chalcone / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004970:Estrone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D002599:Chalcone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases