SYNTHESIS AND STRUCTURAL ELUCIDATION OF BILIARY EXCRETED THIOETHER DERIVATIVES OF MITOXANTRONE

1. Hplc-MS coupling has been used for the identification of thioether derivatives of the anticancer agent mitoxantrone in the bile of pig. 2 . Three biologically relevant new thioether derivatives of mitoxantron e have been synthesized by a horseradish peroxidase-catalysed reaction . 3. The thioether derivatives have been characterized by means of ion spray tandem mass spectrometry and nmr spectrometry including two-dime nsional techniques. 4. The carbon-sulphur bond formation takes place a t the hydroquinone moiety of the anthraquinone skeleton pointing to th e importance of a tautomeric equilibrium between different species of the oxidized drug. 5. The occurrence of the synthesized compounds in b iological systems suggests a metabolic pathway that may be relevant fo r the cytotoxicity of mitoxantrone (oxidative activation).