First evidence that cytochrome P450 may catalyze both S-oxidation and epoxidation of thiophene derivatives

被引：67

作者：

Dansette, PM ^{[1
]}

Bertho, G ^{[1
]}

Mansuy, D ^{[1
]}

机构：

[1] Univ Paris 05, CNRS UMR 8601, UFR Biomed, F-75270 Paris, France

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2005年 / 338卷 / 01期

关键词：

2-phenylthiophene; thiophene-S-oxide dimers; thiophene-S-oxide-glutathione adduct; thiophene epoxide-glutathione adduct; CYP1A1; rat liver microsomes; arene oxide;

D O I：

10.1016/j.bbrc.2005.08.091

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Oxidation of 2-phenylthiophene (2PT) by rat liver microsomes, in the presence of NADPH and glutathione (GSH), led to three kinds of metabolites whose structures were established by H-1 NMR and mass spectrometry. The first ones were 2PT-S-oxide dimers formed by Diels-Alder type dimerization of 2PT-S-oxide, while the second ones were GSH adducts derived from the 1,4-Michael-type addition of GSH to 2PT-S-oxide. The third metabolites were GSH adducts resulting from a nucleophilic attack of GSH to the 4,5-epoxide of 2PT. Oxidation of 2PT by recombinant, human cytochrome P4501A1, in the presence of NADPH and GSH, also led to these three kinds of metabolites. These results provide the first evidence that cytochrome P450 may catalyze the oxidation of thiophene compounds with the simultaneous formation of two reactive intermediates, a thiophene-S-oxide and a thiophene epoxide. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：450 / 455

页数：6

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