Cladosporin, A Highly Potent Antimalaria Drug?

This review summarises recent studies on cladosporin, which is a highly potent inhibitor of the malaria parasite Plasmodium falciparum at the nanomole level that targets lysyl-tRNA synthetase. The chemical synthesis, biosynthesis, the synthesis of analogs, the bioactivity and molecular target, and investigations on the structure-activity relationship are covered.

Abstract

Cladosporin, a unique natural product from the fungus Cladosporium cladosporioides, exhibits nanomolar inhibitory activity against Plasmodium falciparum by targeting its cytosolic lysyl-tRNA synthetase (PfKRS) to inhibit protein biosynthesis. Due to its exquisite selectivity towards pathogenic parasites, cladosporin has become a very promising lead compound for developing antiparasitic drugs to treat drug-resistant malaria and cryptosporidiosis infections. Here we review the recent research progress of cladosporin covering aspects of the chemical synthesis, biosynthesis, bioactivity, cellular target and structure–activity relationship.

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