Evidence for electrophilic properties of N2-methyl-9-hydroxy ellipticinium acetate (Celiptium) from human biliary metabolites.
The human biliary metabolism of the antitumor agent N2-methyl-9-hydroxyellipticinium acetate is described. Three major compounds have been identified by high-performance liquid chromatography and comparison with synthetic reference derivatives: the unchanged drug, the O-glucuronide conjugate and the cysteinyl-ellipticinium adduct. The latter one is the expected detoxification compound of an intermediate electrophilic quinone-imine derivative generated in vivo. This result provides a further evidence that hydroxylated forms of ellipticine derivatives might be activated by a biooxidation route.
D000328:Adult; D000470:Alkaloids / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D004611:Ellipticines / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male
D000470:Alkaloids; D000970:Antineoplastic Agents; D004611:Ellipticines; C027767:elliptinium; D003545:Cysteine