A novel 2-piperazino-pyrimidine compound exhibits asexual antimalarial activity by targeting Plasmodium falciparum plasmepsin X

fold changes similar to those observed in the resistant parasites. Furthermore, FPSA inhibited the proteolytic activity of recombinant PMX in vitro and also the cleavage of PMX substrate proteins in parasites. Transcriptomic analysis confirmed that parasites exposed to FPSA exhibit gene expression patterns similar to those observed in parasites exposed to WM382, a validated plasmepsin IX (PMIX)/PMX dual inhibitor. These results indicate that FPSA inhibits merozoite egress by targeting P. falciparum plasmepsin X. Therefore, this work identifies a novel class of antimalarial compounds that target PMX. Our results are expected to contribute to the development of new drugs for the treatment of malaria.