Exploration of the mechanism of action of alkaloids with antiparasitic activities from Muntafara sessilifolia

Muntafara sessilifolia (Baker) Pichon is an endemic plant of Madagascar whose stem-bark is traditionally used for the treatment of fevers. It was selected based on its inhibitory activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum. Bioassay-guided fractionation on P. falciparum led to the isolation and identification of 26 indole alkaloïds among which 11 were new compounds. Their antifungal activities were also evaluated. A strategy to clarify the modalities of the antiplasmodial action of products with noticeable activities was established. Thus, their hemolytic properties against healthy red blood cells, their inhibitory properties against geographical strains of P. falciparum with different levels of chloroquine sensitivity and the effect of human plasma on their antiplasmodial activity were evaluated. Also, the inhibitory effect of some compounds on the early intraerythrocytic development of P. falciparum was evaluated by optical examination of stained smears. As a result, two compounds, tabernaemontanine acetate and 3'oxotabernaelegantine A, showed interesting biological properties, in particular strain selectivity and late stage targeting. Those preliminary tests can thus be considered as an approach to the mechanism of action of compounds of interest.