کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2597723 | 1562421 | 2007 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Metabolism of 2-substituted quinolines with antileishmanial activity studied in vitro with liver microsomes, hepatocytes and recombinantly expressed enzymes analyzed by LC/MS Metabolism of 2-substituted quinolines with antileishmanial activity studied in vitro with liver microsomes, hepatocytes and recombinantly expressed enzymes analyzed by LC/MS](/preview/png/2597723.png)
Liver microsome and hepatocyte-mediated biotransformation of three oral antileishmanial 2-substituted quinolines were investigated. One quinoline contains an n-propyl group (1) and the other a propenyl chain functionalized at the γ position either by a nitrile (2) or an alcohol (3). The different isoforms of rat cytochrome P450 responsible for biotransformation of 1 were also investigated. Compounds 2 and 3 mainly reacted with glutathione, preventing further metabolism. Compound 3 however, the reaction being reversible, could be released from glutathione and take alternative reaction pathways. Microsomal incubations of 1 mainly led to hydroxylation of the side chain, involving many cytochromes, predominantly CYP2B1, CYP2A6 and CYP1A1 (at more than 80%). In contrary, minor metabolites hydroxylated on the quinoline ring involved a few cytochromes. The hydroxylated products of 1 were conjugated with glucuronic acid in rat hepatocyte incubations.
Journal: Toxicology - Volume 235, Issues 1–2, 3 June 2007, Pages 27–38