Parasitic infections, as malaria, African trypanosomiasis and cutaneaous leishmaniasis, remain one of the main global public health concerns nowadays, despite ongoing efforts. In the crucial research for new antiparasitic treatments, we focused our work on plants used in traditional medicine and their bioactive components. Firstly, we showed, using mice models, the antiparasitic potential and absence of acute toxicity of three plants traditionally used in Benin: Byrsocarpus coccineus (on Trypanosoma brucei), Keetia leucantha (on Plasmodium) and Carpolobia lutea (on both parasites). Given their in vivo antimalarial efficacy, Keetia leucantha twigs were chosen for further researches. The decoction safety was evaluated in different in vivo models (zebrafish embryo, mice acute and repeated-dose toxicity tests) and a part of its antimalarial activity was attributed to the presence of tannins. We then developed validated quantification methods in plant and in plasma for previously identified eight triterpenic esters (27-O-(E/Z)-feruloyl/coumaroyl-oxy-oleanolic/ursolic acids). We also proved their selective in vivo antiplasmodial activities at 50 mg/kg and their involvement in the efficacy of the crude dichloromethane extract of K. leucantha twigs, with other triterpenic acids. Exploring their mechanism of action, we identified the aminopeptidase PfA-M17, implied in the essential haemoglobin degradation pathway, as one potential selective target. Finally, a series of triterpenic acids and esters were screened and compared for in vitro selective antiparasitic activities. Among tested compounds, some semi-synthesized 3-O-aromatic esters showed promising antitrypanosomal activity (IC50 near 2 µM). However, hydrocinnamic and ortho-fluorophenylpropionic ursolic acids, as well as ursolic acid did not improve parasitaemia evolution and survival in an acute trypanosomiasis mice model. This work contributes to the valorization of traditional medicine and to the search for natural antiprotozoal compounds.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201
