Evaluation of ferrocenyl-containing gamma-hydroxy-gamma-lactam-derived tetramates as potential antiplasmodials
Résumé
A series of ferrocenyl-containing gamma-hydroxy-gamma-lactam tetramates were prepared in 2-3 steps through ring opening-ring closure (RORC) process of gamma-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 50 equal to 0.09 µM (3D7) and 0.12 µM (W2). The low cytotoxicity of the ferrocenyl-containing gamma-hydroxy-gamma-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.
Domaines
Chimie organique
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