In vitro oxidative metabolism study of (-)-rhazinilam
In vitro oxidative metabolism study of (-)-rhazinilam
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DOI：
10.1016/j.bmc.2005.10.015
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发表时间：
2006-03-01
影响因子：
3.5
通讯作者：
Baudoin, O
中科院分区：
文献类型：
--
作者：
Décor, A;Bellocq, D;Baudoin, O
进行了代谢研究，以调查体内缺乏活性的（-）-rhazinilam 1，有丝分裂纺锤体的原始毒物的原因。通过球孢白僵菌菌株、大鼠和人肝微粒体的生物转化，可以鉴定在rhazinilam的3和5位氧化的代谢产物2、3和4。进一步的实验表明，CYP 2B 6是人肝微粒体氧化I的主要途径。所有分离的代谢产物在体外的活性明显低于rhazinilam，这可能解释了其在体内的活性。(c)2005爱思唯尔有限公司保留所有权利。
Metabolism studies were conducted in order to investigate the reasons for the in vivo lack of activity of (-)-rhazinilam 1, an original poison of the mitotic spindle. Bioconversion by Beauveria bassiana strains, rat and human liver microsomes allowed the identification of metabolites 2, 3, and 4 oxidized in positions 3 and 5 of rhazinilam. Further experiments indicated that CYP2B6 was the main CYP responsible for the oxidation of I by human liver microsomes. All isolated metabolites were markedly less active than rhazinilam in vitro, which might explain its in vivo inactivity. (c) 2005 Elsevier Ltd. All rights reserved.