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

摘要

Although there are potent antimalarial drugs available, the spread of drug resistance has led to an increase in morbidity and mortality rates in malaria-endemic regions. To overcome these problems, new antimalarial drugs with novel modes of action have to be developed. The recently discovered nonme-valonate pathway of isoprenoid biosynthesis (MEP pathway) is an important metabolic pathway for the design of novel antimalarial drugs. Various pathogenic bacteria (e.g., Mycobacterium tuberculosis) and apicomplexan protozoa (e.g., Plasmodium falciparum) use the MEP pathway for the production of isopen-tenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP).