Journal Article

Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum

Schmitt, Marjorie, Rangel, Gabriel W., Spichty, Martin, Florent, Isabelle, Albrecht, Sebastien, Llinás, Manuel, Frédérich, Michel, Quetin-Leclercq, Joëlle, Beaufay, Claire, Bero, Joanne, Mamede, Lúcia

2026

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aminopeptidase / Analysis / Antimalarial agents / Antimalarials - chemistry / Antimalarials - pharmacology / Antiparasitic agents / Antiprotozoal agents / Biomedical and Life Sciences / Biomedicine / Blood parasites / Care and treatment / Chemical Sciences / Chromatography / Drug development / Entomology / Enzymatic tests / Enzymes / Esters / Esters - pharmacology / Haemoglobin / Health aspects / Hemoglobin / Human diseases / Infectious Diseases / Life Sciences / Malaria / Medicinal Chemistry / Medicinal plants / Metabolism / Metabolomics / Microbiology / Microbiology and Parasitology / Microscopy / Mode of action / Molecular Docking Simulation / Parasites / Parasitic diseases / Parasitology / Parasitoses / PfA-M17 / Pharmaceutical sciences / Pharmacology / Phenolic compounds / Phenols / Phenols - pharmacology / Phenotypes / Phenotypic analysis / Physiological aspects / Plasmodium falciparum / Plasmodium falciparum - drug effects / Plasmodium falciparum - enzymology / Plasmodium spp / Protozoan Proteins - antagonists & inhibitors / Protozoan Proteins - metabolism / Public Health / Testing / Toxicity / Triterpenes - chemistry / Triterpenes - pharmacology / Triterpenic esters / Tropical Medicine / Vector-borne diseases