Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum.
(2026) Malaria Journal — Vol. 25, n° 1, p. 74 [1-11] (2026)
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- BACKGROUND: Malaria is a deadly parasitic disease for which innovative treatments are urgently needed. A mixture of eight triterpenic esters (8TTE) was previously identified as important for the antiplasmodial activity of Keetia leucantha twigs, a plant used in traditional medicine in Benin. Despite the reported in vitro and in vivo activity, the targets of 8TTE are unknown. METHODS: The present study investigated the mode of action of 8TTE on Plasmodium falciparum by a multi-scale integrative study from phenotype to metabolome, including: phenotypic analysis, enzymatic tests, molecular docking and metabolomic profiling. RESULTS: This study identified a unique antiplasmodial profile with activity onset in the early-ring stage of the parasite, the inhibition of aminopeptidase PfA-M17 (PlasmoDB PF3D7_1446200) and perturbations in parasite haemoglobin metabolism. CONCLUSIONS: Further structure-activity and medicinal chemistry studies are warranted to elaborate on these findings and the potential for 8TTE-related molecules to serve as future antimalarial drugs.
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Mamede, L., Rangel, G. W., Schmitt, M., Albrecht, S., Spichty, M., Bero, J., Beaufay, C., Florent, I., Llinás, M., Frédérich, M., & Quetin-Leclercq, J. (2026). Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum. Malaria Journal, 25(1), 74 [1-11]. https://doi.org/10.1186/s12936-025-05762-3 (Original work published 2026)