14α-羟基雄甾-4-烯-3,6,17-三酮作为一种基于机制的雌激素生物合成不可逆抑制剂。

14 alpha-hydroxyandrost-4-ene-3,6,17-trione as a mechanical-based irreversible inhibitor of estrogen biosynthesis.

作者信息

Yoshihama M, Tamura K, Nakakoshi M, Nakamura J, Fujise N, Kawanishi G

机构信息

Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1990 Oct;38(10):2834-7. doi: 10.1248/cpb.38.2834.

DOI:10.1248/cpb.38.2834

PMID:2076569

Abstract

Various derivatives of androst-4-ene-3,17-dione derived from microbial transformation were evaluated as inhibitors of human placental aromatase. 14 alpha-Hydroxyandrost-4-ene-3,6,17-trione was the most potent inhibitor showing a time-dependent, pseudo-first-order inactivation of aromatase in the presence of reduced nicotinamide adenine dinucleotide phosphate with apparent Ki of 1.3 microM and Kinact of 0.23 min-1. This compound also inhibited aromatase in rat ovary and suppressed serum estradiol levels in in vivo experiments.

摘要

对通过微生物转化得到的雄甾-4-烯-3,17-二酮的各种衍生物进行了评估，以确定它们作为人胎盘芳香化酶抑制剂的效果。14α-羟基雄甾-4-烯-3,6,17-三酮是最有效的抑制剂，在还原型烟酰胺腺嘌呤二核苷酸磷酸存在的情况下，它对芳香化酶表现出时间依赖性的假一级失活，表观抑制常数（Ki）为1.3微摩尔，失活速率常数（Kinact）为0.23分钟-1。在体内实验中，该化合物还抑制了大鼠卵巢中的芳香化酶，并降低了血清雌二醇水平。