Combining Stage Specificity and Metabolomic Profiling to Advance Antimalarial Drug Discovery.

ABSTRACT: We report detailed susceptibility profiling of asexual blood stages of the malaria parasite Plasmodium falciparum to clinical and experimental antimalarials, combined with metabolomic fingerprinting. Results revealed a variety of stage-specific and metabolic profiles that differentiated the modes of action of clinical antimalarials including chloroquine, piperaquine, lumefantrine, and mefloquine, and identified late trophozoite-specific peak activity and stage-specific biphasic dose-responses for the mitochondrial inhibitors DSM265 and atovaquone. We also identified experimental antimalarials hitting previously unexplored druggable pathways as reflected by their unique stage specificity and/or metabolic profiles. These included several ring-active compounds, ones affecting hemoglobin catab

SUBMITTER: Murithi JM 

PROVIDER: S-EPMC7031696 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature