Bullion K A, Osawa Y, Braun D G
Endocrine Biochemistry Department, Medical Foundation of Buffalo, Inc., New York 14203.
Endocr Res. 1990;16(2):255-67. doi: 10.1080/07435809009033004.
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.
研究了半琥珀酸双 -（对氰基苯基）咪唑 - 1 - 基甲烷（CGS 18320B）和其他非甾体化合物对人胎盘微粒体芳香化酶催化雄烯二酮芳香化的影响。CGS 18320B表现出竞争性抑制作用，表观抑制常数（Ki）为0.16 nM，与4 - 羟基雄烯二酮和氨鲁米特相比，亲和力分别提高了90倍和3800倍。这种抑制作用不依赖于时间，表明活性位点的相互作用是可逆的。与4 -（5,6,7,8 - 四氢咪唑并[1,5 - a]吡啶 - 5 - 基）苯甲腈（CGS 16949A）和顺式 - 1 - [（4 - [（1 - 咪唑基）甲基]环己基）甲基] - 咪唑琥珀酸盐（CGS 14796C）相比，CGS 18230B的亲和力提高了两倍，后两者的Ki值分别为0.35和0.39μM。1 - [2 - [1 -（4 - 羧基苯基）- 3 - 脲基]乙基] - 2 -（4 - 吡啶基）- 2 - 咪唑啉盐酸盐（CGP 15720A）的抑制作用可忽略不计。
