Research ArticleMalaria

Antimalarial pantothenamide metabolites target acetyl–coenzyme A biosynthesis in Plasmodium falciparum

See allHide authors and affiliations

Science Translational Medicine  18 Sep 2019:
Vol. 11, Issue 510, eaas9917
DOI: 10.1126/scitranslmed.aas9917

Development of a new antimalarial drug

Pantothenenic acid, or vitamin B5, is an essential nutrient for the deadly malaria parasite Plasmodium falciparum. Inhibiting the parasite’s ability to fully metabolize this vitamin using pantothenamide drugs has long been considered a viable antimalarial therapeutic option. Historically, however, pantothenamides have not found success because of an enzyme in human serum that inactivates these molecules. In a new study, Schalkwijk et al. synthesize a series of pantothenamides that contained a modification of the labile bond, rendering them resistant to the action of this enzyme. The authors show that this new class of pantothenamides is converted by the parasite into coenzyme A analogs that are highly potent against malaria parasites at multiple stages of the Plasmodium life cycle.

View Full Text

Stay Connected to Science Translational Medicine