Fiche publication
Date publication
décembre 2024
Journal
ChemMedChem
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIOUD-CHARVET Elisabeth
,
Dr ELHABIRI Mourad
Tous les auteurs :
Dupouy B, Karpstein T, Häberli C, Cal M, Rottmann M, Maeser P, Keiser J, Elhabiri M, Davioud-Charvet E
Lien Pubmed
Résumé
This study explores the synthesis and evaluation of novel 1,2,3-triazole-methyl-1,4-naphthoquinone hybrids, focusing on their electrochemical properties and antiparasitic efficacies against two human blood-dwelling parasites Plasmodium falciparum and Schistosoma mansoni. Using copper-catalyzed azide-alkyne cycloaddition (CuAAC), a well-established tool in click chemistry, two synthetic routes were assessed to develop a- and b-[triazole-methyl]-menadione derivatives. By optimizing the CuAAC reaction conditions, yields were significantly improved, reaching up to 94% for key intermediates and resulting in the formation of a library of approximately 30 compounds. Biological evaluation of the compounds in antiparasitic drug assays demonstrated notable antischistosomal potencies, while no significant activity was observed for the same series against P. falciparum parasites. Electrochemical and 'benzylic' oxidation studies confirmed that the active 'benzoyl' metabolite responsible for the antiplasmodial activity of plasmodione cannot be generated. These findings highlight the potential of triazole-linked menadione hybrids as promising early candidates for antischistosomal drug development, and provides insights into structure-activity relationships crucial for future therapeutic strategies.
Mots clés
Click chemistry (or CuAAC) * plasmodione * 1,2,3-triazole * Plasmodium falciparum * Schistosoma mansoni
Référence
ChemMedChem. 2024 12 16;:e202400731