Aromatase and 17β-hydroxysteroid dehydrogenase inhibition by flavonoids

A method for estimating in the same assay both aromatase and 17 beta-hydroxysteroid dehydrogenase activities in human placental microsomes using radiolabelled [1,2,6,7-H-3]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 beta-hydroxysteroid dehydrogenase was studied. Flavonoids were shown to be potent inhibitors of both aromatase and 17 beta-hydroxysteroid dehydrogenase activities. We found that 7-hydroxyflavone and apigenin are the most effective aromatase and 17 beta-hydroxysteroid dehydrogenase inhibitors, respectively. Experiments showed that a hydroxyl group in position 7 was essential for anti-17 beta-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. (C) 1998 Elsevier Science ireland Ltd. All rights reserved.