Thiazole substitution of a labile amide bond-a new option toward antiplasmodial pantothenamide-mimics.

ABSTRACT: The emergence and spread of artemisinin-partial resistant, malaria-causing Plasmodium falciparum provide the impetus for developing novel antimalarials. Pantothenamides are potent inhibitors of malaria parasite proliferation; however, their clinical use is hindered by pantetheinase-mediated degradation in human serum. Here, we report the synthesis and biological activity of a series of pantothenamide-mimics in which the thiazole ring replaces the labile amide bond with various orientations. Out of 23 novel compounds generated and tested in the presence of pantetheinase, several display sub-micromolar antiplasmodial activity in vitro. A selection of compounds was studied in more detail, and CoA biosynthesis and/or utilization pathways were confirmed to be the target. Toxicity

SUBMITTER: Liu X 

PROVIDER: S-EPMC12406685 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature