The Design, Synthesis and Evaluation of Novel Metalloaminopeptidase Inhibitors

Approximately 247 million infections and 619,000 deaths associated with malaria were recorded in 2021. Malaria caused by Plasmodium falciparum has two enzymes, PfA-M1 and PfA-M17, which play vital roles in the fitness and survival of malaria parasites. Inhibition of PfA-M1 and PfA-M17 results in parasite death. Using the structures of PfA-M1 and PfA-M17, a range of new inhibitors were designed, synthesised, and evaluated for use as potential antimalarial agents. Several of these new compounds were found to be potent inhibitors of PfA-M1 and inhibited malaria parasites, with this work paving the way towards a new class of antimalarial therapy.