Evidence for electrophilic properties of N 2 -methyl-9-hydroxy ellipticinium acetate (Celiptium) from human biliary metabolites

Summary 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.Part of this work was done by J. B. as part of his preparation for the degree of Doctor of Medicine in the Centre Claudius Regaud