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[细胞色素P-450底物结构的定向修饰作为生成微粒体单加氧酶系统新诱导剂的一种方法]

[Directed modification of the structure of cytochrome P-450 substrates as a method of generating new inducers of the microsomal monooxygenase system].

作者信息

Tsyrlov I B, Gerasimov K E, Gutkina N I, Liakhovich V V

出版信息

Biokhimiia. 1987 Aug;52(8):1307-14.

PMID:3663765
Abstract

Using the previously obtained data on the substrate-type induction of monooxygenase by xenobiotics of phenobarbital type, the method of conversion of typical substrates for cytochrome P-450 into inducers of biosynthesis of this enzymatic system by blocking in the substrate molecule of the position subjected to oxidative conversion in the enzyme active center was tested. The introduction of the methyl group in the omega-1 position of amobarbital, of Cl- into positions 2 and 4 of biphenyl and the substitution of methyl groups for the isopropyl groups in the 4-N(CH3)2 position of aminopyrine provides for marked induction of these derivatives of cytochrome P-450 and some monooxygenase activities.

摘要

利用先前获得的关于苯巴比妥型异生物质对单加氧酶底物类型诱导作用的数据,测试了通过阻断底物分子中酶活性中心进行氧化转化的位置,将细胞色素P - 450的典型底物转化为该酶系统生物合成诱导剂的方法。在异戊巴比妥的ω-1位引入甲基、在联苯的2位和4位引入氯以及在氨基比林的4 - N(CH3)2位用异丙基取代甲基,可显著诱导细胞色素P - 450的这些衍生物以及一些单加氧酶活性。

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