Triazole Substitution of a Labile Amide Bond Stabilizes Pantothenamides and Improves Their Antiplasmodial Potency.

ABSTRACT: The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC₅₀s) of ∼50 nM, and three others have submicromolar IC₅₀s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds f

SUBMITTER: Howieson VM 

PROVIDER: S-EPMC5118993 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature