Malaria journal · 2026
Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum.
СтатьяНазвание и аннотация: Перевод в очереди
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Mamede Lúcia, Rangel Gabriel W, Schmitt Marjorie, Albrecht Sebastien, Spichty Martin, Bero Joanne, Beaufay Claire, Florent Isabelle, Llinás Manuel, Frédérich Michel, Quetin-Leclercq Joëlle
Аннотация
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.
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.