氨鲁米特对映体及类似物对芳香化酶的体外抑制作用。

In vitro inhibition of aromatase by the enantiomers of aminoglutethimide and analogs.

作者信息

Ogbunude P O, Aboul-Enein H Y

机构信息

Department of Biological and Medical Research (MBC-03), King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

出版信息

Chirality. 1994;6(8):623-6. doi: 10.1002/chir.530060804.

DOI:10.1002/chir.530060804

PMID:7857773

Abstract

The in vitro aromatase activity in microsomal fractions from rat ovary and its inhibition by enantiomers of aminoglutethimide (AG), rogletimide (RG), and cyclohexylaminoglutethimide (ChAG) were studied by analysing the [3H]H2O released when [1 beta-3H]androstenedione was converted to estrone. Maximum velocity (Vmax) and the Michaelis-Menten constant (Km) of the microsomal aromatase enzyme were 17.40 +/- 0.45 pmol/ml/mg protein/min and 1.02 +/- 0.06 microM, respectively. The IC50s for the enantiomers were similar for (+)-R-AG and (-)-R-ChAG (0.86 +/- 0.06 and 0.89 +/- 0.15 microM, respectively. (+)S-ChAG was most potent with IC50 of 0.075 +/- 0.003 microM. The IC50s for (-)-S-AG, (+)-R-RG, and (-)-S-RG were in the same range (23.15 +/- 2.74, 24.58 +/- 2.46, and 24.43 +/- 2.20 microM, respectively.

摘要

通过分析[1β-3H]雄烯二酮转化为雌酮时释放的[3H]H2O，研究了大鼠卵巢微粒体部分的体外芳香化酶活性及其受氨鲁米特（AG）、罗格列米特（RG）和环己基氨鲁米特（ChAG）对映体的抑制作用。微粒体芳香化酶的最大反应速度（Vmax）和米氏常数（Km）分别为17.40±0.45 pmol/ml/mg蛋白/分钟和1.02±0.06微摩尔。（+）-R-AG和（-）-R-ChAG对映体的半数抑制浓度（IC50）相似（分别为0.86±0.06和0.89±0.15微摩尔）。（+）-S-ChAG最有效，IC50为0.075±0.003微摩尔。（-）-S-AG、（+）-R-RG和（-）-S-RG的IC50在同一范围内（分别为23.15±2.74、24.58±2.46和24.43±2.20微摩尔）。