Reversible inhibition of human placental microsomal aromatase by CGS 18320B and other non-steroidal compounds

The effect of bis-(p-cyanophenyl)imidazo-1-yl-methane hemisuccinate (CGS 18320B) and other non-steroidal compounds on the aromatization of androstenedione by human placental microsomal aromatase was studied. CGS 18320B exhibited competitive inhibition with an apparent Ki of 0.16 nM, a 90 and 3800-fold increase in affinity compared to 4-hydroxyandrostenedione and amino-glutethimide, respectively. The inhibition is not time-dependent, indicating that the active site interaction is reversible. CGS 18230B showed a two-fold increased affinity as compared to 4-(5,6,7,8-tetrahydroimidazo[1,5a]pyridin-5-yl)benzonitrile (CGS 16949A) and cis-1-[(4-[(1-imidazoyl)methyl]cyclohexyl)methyl]-imidazole succinate (CGS 14796C) which showed Ki values of 0.35 and 0.39 4M, respectively. 1-[2-[1-(4-carboxyphenyl)-3-ureido]ethyl]-2-(4-pyridyl)-2-imidazoline monohydrochloride (CGP 15720A) showed negligible inhibition.