Inhibition of rat liver microsomal cytochrome P-450 steroid hydroxylase reactions by imidazole antimycotic agents.
Inhibition of rat liver microsomal cytochrome P-450 steroid hydroxylase reactions by imidazole antimycotic agents.
复制标题
咪唑抗真菌剂抑制大鼠肝微粒体细胞色素 P-450 类固醇羟化酶反应。
DOI：
10.1016/0006-2952(86)90224-8
复制
发表时间：
1986
影响因子：
5.8
通讯作者：
Estabrook,RW
中科院分区：
文献类型：
--
作者：
Sheets,JJ;Mason,JI;Wise,CA;Estabrook,RW
咪唑类抗真菌药酮康唑、咪康唑和克霉唑通过大鼠肝微粒体细胞色素P-450检测其抑制雄甾-4-烯-3，17-二酮氧化代谢反应的能力。所有三种化合物都被发现是类固醇羟化酶反应的有效抑制剂，在10− 7和K− 5 M之间的浓度下，对6β-、16β-和16α-羟化酶活性产生50%的抑制。当加入肝微粒体中时，抗霉菌剂以高亲和力与细胞色素P-450结合，产生“II型”光谱复合物。这些药物对各种类固醇羟化酶的抑制作用不同，并且发现不影响肝微粒体类固醇5α-还原酶或雄甾-4-烯-3，17-二酮17-氧化还原酶的活性。结果表明，这些咪唑抗霉菌剂与肝微粒体的各种细胞色素P-450的相互作用，导致单加氧酶活性的选择性抑制。
The imidazole antimycotic agents ketoconazole, miconazole and clotrimazole were tested for their abilities to inhibit the reactions involved in the oxidative metabolism of androst-4-ene-3,17-dione by rat liver microsomal cytochromes P-450. All three compounds were found to function as potent inhibitors of steroid hydroxylase reactions, producing 50% inhibition of 6β-, 16β-, and 16α-hydroxylase activities at concentrations between 10−7and K−5M. The antimycotic agents, when added to liver microsomes, bound to cytochrome P-450 with high affinity to produce a “type II” spectral complex. These agents showed differential inhibition of the various steroid hydroxylases and were found not to affect the activities of the liver microsomal steroid 5α-reductase or the androst-4-ene-3,17-dione 17-oxidoreductase. The results presented demonstrate an interaction of these imidazole antimycotic agents with the various cytochromes P-450 of liver microsomes, resulting in selective inhibition of monooxygenase activity.