New synthetic flavones of natural origin as antimalarial agents

Recent reports of increased tolerance to artemisinin derivatives, the most recently adopted class of antimalarials, have prompted a need for new treatments. In this context, we tested the antimalarial activity of lanaroflavone, a biflanonoid isolated from the methanol extract of the aerial part of Campnosperma panamense Standl. (Anacardiaceae), an endemic tree species of Colombia (1). Lanaroflavone showed good in vitro antimalarial activity but was inactive in a rodent model.

Here, 10 new simplified synthetic analogs of lanaroflavone were tested for the first time against blood stage culture of different chloroquine sensitive and resistant strains of P. falciparum (3D7, Africa and 7G8, Brazil). We used immunoenzymatic technique based on the Plasmodium Lactate Deshydrogenase production to evaluate the inhibition of parasitic growth and to determine the target stage throughout the erythrocytic cycle of Plasmodium. Haemotoxicity and cytotoxicity were also evaluated.

Out of the 10 compounds tested, MR27770 strongly killed the early blood stages of P. falciparum at nanomolar concentrations. We noted no haemolytic effect in vitro on red blood cells or cytotoxicity on several cultured cell lines (hepatic mouse cells Hepa 1–6 and Normal Human Dermal Fibroblasts), with selectivity indexes values above 1000. Evaluation of MR27770 in a rodent malaria model will also be presented.

References: 1. Weniger et al. (2006) Phytomedicine 13: 176–180