Covalent Inhibitors of Plasmodium falciparum Glyceraldehyde 3-Phosphate Dehydrogenase with Antimalarial Activity in Vitro

Covalent inhibitors of PfGAPDH characterized by a 3-bromoisoxazoline warhead were developed, and their mode of interaction with the target enzyme was interpreted by means of molecular modeling studies: some of them displayed a submicromolar antiplasmodial activity against both chloroquine sensitive and resistant strains of Plasmodium falciparum, with good selectivity indices.