Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum.

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.