Synthesis and Antiplasmodial Activity of Highly Active Reverse Analogues of the Antimalarial Drug Candidate Fosmidomycin

Inhibition of enzymes involved in the nonmevalonate pathway of isoprenoid biosynthesis represents a promising strategy for the development of novel antimalarial agents. A small series of reverse hydroxamate‐based fosmidomycin analogues was synthesized and evaluated for their inhibitory activity against the recombinant 1‐deoxy‐D‐xylulose 5‐phosphate reductoisomerases (DXRs) of Escherichia coli and Plasmodium falciparum, as well as for their in vitro antiplasmodial activity and cytotoxicity.