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

Date publication

avril 2018

Journal

Organic & biomolecular chemistry

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DAVIOUD-CHARVET Elisabeth

Tous les auteurs :
Feng L, Lanfranchi DA, Cotos L, Cesar-Rodo E, Ehrhardt K, Goetz AA, Zimmermann H, Fenaille F, Blandin SA, Davioud-Charvet E

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29542786

Résumé

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.

Référence

Org. Biomol. Chem.. 2018 Apr 18;16(15):2647-2665