Several extracts of Annona senegalensis (Annonaceae) seeds were tested for antiparasitic activity against Leishmania major, Leishmania donovani, Trypanosoma brucei brucei, and for cytotoxic activity against KB and VERO cell lines. Fractionation of seeds extracts was mainly guided by means of a biocidal assay against Artemia salina nauplii. The biological activities resulted from extract-isolated acetogenins.

Summary:lr-(COD)-pentamidine tetraphenylborate which has previously been studied on promastigote forms of Leishmania, was investigated for its antileishmanial properties compared with pentamidine used as reference compound. In vitro, the iridium complex had the same IC 50 value on intracellular forms of Leishmania as pentamidine (15 µM). In vivo, the compound could not be injected intravenously due to the DMSO excipient so that the treatments were performed intraperitoneally or subcutaneously. On the L. donovani LV9 /Balb/C mouse model, the iridium complex was not toxic after intraperitoneal treatment at 232 mg/kg/day x 5 or 147 µmoles/ kg/day x 5, whereas all the mice died within five days when treated at the same dose with pentamidine isethionate. However, only 23 % of parasite suppression was observed with the iridium complex. On a L. major MON 74/Balb/C mouse model, susceptible to intravenously administered pentamidine at 6.7 umoles/ kg/day x 5 (54 % of parasite suppression), the iridium complex exhibited 32 % of parasite suppression after a treatment at 76 umoles/ kg/day x 5 administered subcutaneously. This slight activity is of interest since pentamidine isethionate is not active under these conditions. Transmission electron microscopy of amastigotes from infected and treated mice show aggregation of ribosomal material, distension of the nuclear membrane and kDNA depolymerization. The mechanism of action therefore involves several targets: membranes, ribosomes and kDNA. According to our results, the Iridium complex is a suitable candidate to be encapsulated in drug carriers such as liposomes or nanoparticles.KEYWORDS : Iridium pentamidine complex, pentamidine, Leishmania, electron microscopy, mechani sm of action. MOTS CLÉS

After ethnobotanical surveys in central and western regions of Burkina Faso, five plants namely Lantana ukambensis (Verbenaceae), Xeoderris sthulmannii (Fabaceae), Parinari curatellifollia (Chrysobalanaceae), Ozoroa insignis (Anacardiaceae), and Ficus platyphylla (Moraceae) were selected for their traditional use in the treatment of parasitic diseases and cancer. Our previous studies have focused on the phytochemical, genotoxicity, antioxidant, and antiproliferative activities of these plants. In this study, the methanol extract of each plant was tested to reveal probable antileishmanial and antitrypanosomal activities. Colorimetric and spectrophotometric methods were used for the detection of antileishmanial and antitrypanosomal activities. Leishmania donovani (LV9 WT) and Trypanosoma brucei brucei GVR 35 were used to test the antileishmanial and antitrypanosomal activities, respectively. All extracts of tested plants showed a significant antitrypanosomal activity with minimum lethal concentrations between 1.5 and 25 μg/ml, the L. ukambensis extract being the most active. In the antileishmanial test, only the extract from L. ukambensis showed significant activity with an inhibitory concentration (IC(50)) of 6.9 μg/ml. The results of this study contribute to the promotion of traditional medicine products and are preliminary for the isolation of new natural molecules for the treatment of leishmaniasis and trypanosomiasis.

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