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Synthesis of plasmodione metabolites and 13C-enriched plasmodione as chemical tools for drug metabolism investigation

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Zimmermann,  Herbert
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

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引用

Feng, L., Lanfranchi, D. A., Cotos, L., Cesar-Rodo, E., Ehrhardt, K., Goetz, A.-A., Zimmermann, H., Fenaille, F., Blandin, S. A., & Davioud-Charvet, E. (2018). Synthesis of plasmodione metabolites and 13C-enriched plasmodione as chemical tools for drug metabolism investigation. Organic & Biomolecular Chemistry, 16(15), 2647-2665. doi:10.1039/C8OB00227D.


引用: https://hdl.handle.net/21.11116/0000-0001-2E6E-2
要旨
Malaria is a tropical parasitic disease threatening populations in tropical and sub-tropical areas. Resistance to antimalarial drugs has spread all over the world in the past 50 years, thus new drugs are urgently needed. Plasmodione (benzylmenadione series) has been identified as a potent antimalarial early lead drug, acting through a redox bioactivation on asexual and young sexual blood stages. To investigate its metabolism, a series of plasmodione-based tools, including a fully 13C-labelled lead drug and putative metabolites, have been designed and synthesized for drug metabolism investigation. Furthermore, with the help of UHPLC-MS/MS, two of the drug metabolites have been identified from urine of drug-treated mice.