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 mitoxantrone 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-dimensional techniques. 4. The carbon-sulphur bond formation takes place at the hydroquinone moiety of the anthraquinone skeleton pointing to the importance of a tautomeric equilibrium between different species of the oxidized drug. 5. The occurrence of the synthesized compounds in biological systems suggests a metabolic pathway that may be relevant for the cytotoxicity of mitoxantrone (oxidative activation).
Mewes
K
K
Institut für Organische Chemie, Universität Tübingen, Germany.
Blanz
J
J
Freund
S
S
Ehninger
G
G
Zeller
K P
KP
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004987:Ethers / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008942:Mitoxantrone / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature
D004987:Ethers; D013438:Sulfhydryl Compounds; D013455:Sulfur; D002244:Carbon; D008942:Mitoxantrone; D006735:Horseradish Peroxidase