Inhibitors of plasmepsin II - Potential antimalarial agents

Abstract

Malaria is a very serious infectious disease affecting over two billion people worldwide. Currently available antimalarial drugs are losing effectiveness due to the emergence and the spread of resistant parasite strains. In order to regain control over the disease, new treatments are urgently needed. Drug discovery efforts in this direction are most likely to be successful if they target a novel mechanism of action. Such approaches will lead to antimalarial medicines that are functionally and structurally different from the existing drugs and therefore will have the potential to overcome existing resistances. Our own efforts are focused on the aspartic protease plasmepsin II (PMII) which is a promising new drug target for future antimalarial therapies. We have found structurally simple, moderately active, non-peptide inhibitors of plasmepsin II which offer ample opportunity for further optimization efforts.