In vitro oxidative metabolism study of (−)-rhazinilam

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 1 by human liver microsomes. All isolated metabolites were markedly less active than rhazinilam in vitro, which might explain its in vivo inactivity.

Figure optionsDownload as PowerPoint slide