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

Abstract

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. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.