Synthesis of protease inhibitors derivatives

Malaria accounts for more than a million deaths each year, Plasmodium falciparum is the most dangerous form of the four malarial parasites that infect humans. A particular family of aspartic proteases, known as the plasmepsins, appears to be involved in the initial steps of the degradation of hemoglobin which provides nutrients for its growth and maturation of parasite. This degradation of hemoglobin is one of the critical stages of the life cycle of the Plasmodium during human infection, so it was an attractive antimalarial drug target. A secondary alcohol is usually the structural element of choice to inhibit aspartic protease. This element mimics the tetrahedral intermediate during peptide bond cleavage by aspartic proteases. Recently, we published the antimalarial (Figure 1) 1 and tuberculostatic 2 activities of protease hydroxyethylamine-based inhibitors. In this work, we report the synthesis of novel protease inhibitors derivatives that have potential antimalarial activity.