Androst-5-ene-7,17-dione: a novel class of suicide substrate of aromatase.
5-En-7-one steroid 1 was found to be a potent inhibitor of aromatase. This along with its 19-hydroxy derivative 7 was characterized as suicide substrate of human placental aromatase (k(inact)'s of 0.069 and 0.058 min-1 and KI's of 143 nM and 11.1 microM, respectively, for steroids 1 and 7). The results suggest that the 19-oxygenation would be involved in the irreversible inactivation of aromatase by the 5-en-7-one steroids.
Numazawa
M
M
Tohoku College of Pharmacy, Sendai, Japan.
Mutsumi
A
A
Hoshi
K
K
Tanaka
Y
Y
D000735:Androstenedione / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001667:Binding, Competitive; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008861:Microsomes / Q000201:enzymology; D015394:Molecular Structure; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013379:Substrate Specificity
D047072:Aromatase Inhibitors; D007202:Indicators and Reagents; D000735:Androstenedione; D001141:Aromatase