A photoaffinity inhibitor of aromatase.
Several 7 alpha-substituted 4-androstene-3,17-diones are potent inhibitors of the biosynthesis of estrogens, with the most effective being 7 alpha-(4'-amino)phenylthio-4-androstene-3,17-dione. An azide derivative of this 7 alpha-thioether compound has been prepared as a potential photoaffinity inhibitor. The enzyme kinetics of the azide analog were examined under both dark conditions and UV irradiation. In the dark, the azide was a very potent competitive inhibitor, with an apparent Ki of 1.3 nM. Under UV-irradiation, a time-dependent loss of aromatase activity was also observed. These studies indicate that the 7 alpha-substituent enhances the affinity of the steroidal analogs for the enzyme site.
D000345:Affinity Labels; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D001141:Aromatase / Q000528:radiation effects; D047072:Aromatase Inhibitors; D005260:Female; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D008861:Microsomes / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
D000345:Affinity Labels; D047072:Aromatase Inhibitors; D000735:Androstenedione; C028626:7-(4'-amino)phenylthioandrostenedione; D010088:Oxidoreductases; D001141:Aromatase