[en] ABSTRACT: BACKGROUND: Natural products could play an important role in the challenge to discover new anti-malarial drugs. In a previous study, Dicoma tomentosa (Asteraceae) was selected for its promising anti-plasmodial activity after a preliminary screening of several plants traditionally used in Burkina Faso to treat malaria. The aim of the present study was to further investigate the antiplasmodial properties of this plant and to isolate the active anti-plasmodial compounds. METHODS: Eight crude extracts obtained from D. tomentosa whole plant were tested in vitro against two Plasmodium falciparum strains (3D7 and W2) using the p-LDH assay (colorimetric method). The Peters' four-days suppressive test model (Plasmodium berghei-infected mice) was used to evaluate the in vivo anti-plasmodial activity. An in vitro bioguided fractionation was undertaken on a dichloromethane extract, using preparative HPLC and TLC techniques. The identity of the pure compound was assessed using UV, MS and NMR spectroscopic analysis. In vitro cytotoxicity against WI38 human fibroblasts (WST-1 assay) and haemolytic activity were also evaluated for extracts and pure compounds in order to check selectivity. RESULTS: The best in vitro anti-plasmodial results were obtained with the dichloromethane, diethylether, ethylacetate and methanol extracts, which exhibited a high activity (IC50 [less than or equal to] 5 mug/ml). Hot water and hydroethanolic extracts also showed a good activity (IC50 [less than or equal to] 15 mug/ml), which confirmed the traditional use and the promising anti-malarial potential of the plant. The activity was also confirmed in vivo for all tested extracts. However, most of the active extracts also exhibited cytotoxic activity, but no extract was found to display any haemolytic activity. The bioguided fractionation process allowed to isolate and identify a sesquiterpene lactone (urospermal A-15-O-acetate) as the major anti-plasmodial compound of the plant (IC50 < 1 mug/ml against both 3D7 and W2 strains). This was also found to be the main cytotoxic compound (SI =3.3). While this melampolide has already been described in the plant, this paper is the first report on the biological properties of this compound. CONCLUSIONS: The present study highlighted the very promising anti-plasmodial activity of D. tomentosa and enabled to identify its main active compound, urospermal A-15-O-acetate. The high antiplasmodial activity of this compound merits further study about its anti-plasmodial mechanism of action. The active extracts of D. tomentosa, as well as urospermal A 15-Oacetate, displayed only a moderate selectivity, and further studies are needed to assess the safety of the use of the plant by the local population.