Discovery of oxybisbenzoylamides as a new class of antimalarial agents

Abstract

We have previously described several potent dual inhibitors of Plasmodium falciparum (Pf) growth characterized by the presence of statine, a β-hydroxyl amino acid able to inhibit parasite's plasmepsins (PLMs). While investigating the mechanism of action of these inhibitors, new compounds derived from statine were synthesized, which lost the ability to inhibit PLMs, but retained a significant Pf growth inhibition. Further structural simplifications showed that the inhibition of Pf viability was ascribed to a new pharmacophore never described before as antimalarial.