Evaluation of ferrocenyl-containing γ-hydroxy-γ-lactam-derived tetramates as potential antiplasmodials.
Fiche publication
Date publication
septembre 2022
Journal
European journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIOUD-CHARVET Elisabeth , Dr ELHABIRI Mourad
Tous les auteurs :
Chopin N, Bosson J, Iikawa S, Picot S, Bienvenu AL, Lavoignat A, Bonnot G, Riou M, Beaugé C, Guillory V, Biot C, Pilet G, Chessé M, Davioud-Charvet E, Elhabiri M, Bouillon JP, Médebielle M
Lien Pubmed
Résumé
A series of ferrocenyl-containing γ-hydroxy-γ-lactam tetramates were prepared in 2-3 steps through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of ferrocenyl alkylamines. The compounds were screened in vitro for their antiplasmodial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (W2) clones of P. falciparum, displaying activity in the range of 0.12-100 μM, with generally good resistance index. The most active ferrocene in these series exhibited IC equal to 0.09 μM (3D7) and 0.12 μM (W2). The low cytotoxicity of the ferrocenyl-containing γ-hydroxy-γ-lactam tetramates against Human Umbilical Vein Endothelial (HUVEC) cell line demonstrated selective antiparasitic activity. The redox properties of these ferrocene-derived tetramates were studied and physico-biochemical studies evidenced that these derivatives can exert potent antimalarial activities via a mechanism distinct from ferroquine.
Mots clés
Antimalarial, Fenton, Ferrocene, Lactam, ROS, Tetramate
Référence
Eur J Med Chem. 2022 09 12;243:114735