Anti-African trypanocidal and antimalarial activity of natural flavonoids, dibenzoylmethanes and synthetic analogues

Objectives The known anti-protozoal activity of flavonoids has stimulated the testing of other derivatives from natural and synthetic sources. Methods As part of our efforts to find potential lead compounds, a number of flavonoids isolated from Neoraputia paraensis, N. magnifica, Murraya paniculata, (Rutaceae), Lonchocarpus montanus, L. latifolius, L. subglaucescens, L. atropurpureus, L. campestris, Deguelia hatschbachii (Leguminosae), dibenzoylmethanes from L. subglaucescens and synthetic analogues were tested for in-vitro activity against chloroquine-sensitive Plasmodium falciparum and Trypanosoma brucei rhodesiense bloodstream form trypomastigotes. An assay with KB cells has been developed in order to compare in-vitro cytotoxicity of flavonoids with a selective action on the parasites. Key findings Thirteen of the compounds tested had IC50 values ranging from 4.6 to 9.9 is a subset of M against T. brucei rhodesiense. In contrast, a small number of compounds showed significant activity against P. falciparum; seven of those tested had IC50 values ranging from 2.7 to 9.5 is a subset of M. Among the flavones only one had IC50 < 10 is a subset of M (7.6 is a subset of M), whereas against T. brucei rhodesiense seven had IC50 < 10 is a subset of M. Synthetic dibenzoylmethanes were the most active in terms of number (five) of compounds and the IC50 values (2.7-9.5 is a subset of M) against P. falciparum. Conclusions Dibenzoylmethanes represent a novel class of compounds tested for the first time as antimalarial and trypanocidal agents.