Aromatase and 17β-hydroxysteroid dehydrogenase inhibition by flavonoids

Abstract A method for estimating in the same assay both aromatase and 17 β -hydroxysteroid dehydrogenase activities in human placental microsomes using radiolabelled [1,2,6,7- 3 H]4-androstene-3,17-dione was proposed. In this assay, estrone (E 1 ) and estradiol (E 2 ) produced were separated by HPLC and estimated using a radioactive flow detector. Using this method, the inhibitory effect of various flavonoids, including flavone, flavanone and isoflavone, on the human placental aromatase and 17 β -hydroxysteroid dehydrogenase was studied. Flavonoids were shown to be potent inhibitors of both aromatase and 17 β -hydroxysteroid dehydrogenase activities. We found that 7-hydroxyflavone and apigenin are the most effective aromatase and 17 β -hydroxysteroid dehydrogenase inhibitors, respectively. Experiments showed that a hydroxyl group in position 7 was essential for anti-17 β -hydroxysteroid dehydrogenase activity. However, flavonoids with 7-methoxy or 8-hydroxyl groups on the A ring showed only anti-aromatase activity. Structure–activity relationships were discussed.