Evaluation of 7-hydroxy-flavones as inhibitors of oestrone and oestradiol biosynthesis.
A series of 4-aryl substituted 7-hydroxy-flavones were prepared using the three-step Baker-Venkataraman synthesis in good overall yields. The flavones were all evaluated in vitro for inhibitory activity against aromatase (P450AROM, CYP19), using human placental microsomes, and for inhibitory activity against 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD-1) using human placental cytosol. The phenyl, 4-fluoro-phenyl and 4-bromo-phenyl derivatives displayed moderate inhibitory activity against P450AROM (IC50 17.2, 13.5 and 10.1 microM, respectively), none of the flavones, including the standard genistein, displayed any inhibitory activity against 17beta-HSD type 1 at 100 microM concentration.
Vinh
T K
TK
Medicinal Chemistry Division, Welsh School of Pharmacy, Cardiff University, UK.
Nicholls
P J
PJ
Kirby
A J
AJ
Simons
C
C
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D047072:Aromatase Inhibitors; D003600:Cytosol / Q000201:enzymology; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000096:biosynthesis; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D004970:Estrone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005260:Female; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008861:Microsomes / Q000201:enzymology; D010920:Placenta
D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D005419:Flavonoids; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; C429845:7-hydroxyflavone