Numazawa M, Mutsumi A, Tachibana M, Nagaoka M
Tohoku College of Pharmacy, Sendai, Japan.
Biol Pharm Bull. 1995 Apr;18(4):555-8. doi: 10.1248/bpb.18.555.
19-Nor (2) and 5 alpha-reduced (3) derivatives of androst-4-ene-3,6,17-trione (1) as well as 5 alpha-androstan-17-ones 4-6 were tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids except 5 alpha-6-one 4 were fair to good competitive inhibitors of the enzyme, with apparent Ki's ranging from 50 to 820 nM in which 5 alpha-3-one 5 was the most potent among them. The inhibitory activities of the 19-nor and 5 alpha-reduced derivatives (2 and 3) were less potent than that of the parent compound 1. Inhibitor 2 caused a time-dependent, pseudo-first-order inactivation of aromatase activity with a rate constant for inactivation of 0.148 min-1 in the presence of NADPH in air. The substrate androstenedione prevented the inactivation and L-cysteine did not protect aromatase from the inactivation.
对雄甾-4-烯-3,6,17-三酮（1）的19-去甲（2）和5α-还原（3）衍生物以及5α-雄甾烷-17-酮4 - 6进行了测试，以考察它们抑制人胎盘微粒体中芳香化酶的能力。除5α-6-酮4外，所有甾体对该酶均为中等至良好的竞争性抑制剂，表观解离常数（Ki）在50至820 nM之间，其中5α-3-酮5是其中活性最强的。19-去甲和5α-还原衍生物（2和3）的抑制活性低于母体化合物1。在空气中存在NADPH的情况下，抑制剂2导致芳香化酶活性呈时间依赖性的假一级失活，失活速率常数为0.148 min⁻¹。底物雄烯二酮可防止失活，而L-半胱氨酸不能保护芳香化酶免于失活。
