A Novel Antimalarial Agent that Inhibits Protein Synthesis in Plasmodium falciparum.

ABSTRACT: The emergence of drug resistance to nearly all antimalarials following their rollout underscores the need for novel chemotypes with novel modes of action to replenish the antimalarial drug-development pipeline. We identified a novel class of compounds in the antimalarial armory. Compound 31, characterized by a 2-hydroxyphenyl benzamide scaffold, displays potent activity against blood-stage and mature sexual stages of Plasmodium falciparum and no toxicity in human cells. Resistance selection studies with 31 identified a previously unknown point mutation in the P. falciparum multidrug-resistance protein 1 (pfmdr1) gene, for which we confirmed causality by CRISPR/Cas9-based gene editing as the primary mediator of resistance. No cross-resistance toward first-line antimalarials was identified i

SUBMITTER: Bravo P 

PROVIDER: S-EPMC12668308 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature