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.