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Recherche de nouvelles molécules trypanocides

Abstract : Kinetoplastid diseases are vectorial parasitoses caused by flagellated blood protozoa. Among these, African Trypanosomiasis, due to a parasite of the genus Trypanosoma, affects both humans and animals. In humans, this disease, known as sleeping sickness, progresses classically in 2 stages: the hemolymphatic stage characterized by multiplication of the parasite in blood and lymph and the nervous stage characterized by the presence of the parasite in the brain. In the absence of appropriate therapy, death is inevitable. Currently, the treatments proposed in human and veterinary medicine are old, toxic and at the origin of cases of resistance. The search for new molecules is therefore essential to control this pathology. It is in this context that we studied two families of molecules which recognize parasitic sites: (i) Nitroimidazoles that interact with nitroreductases to generate toxic intermediates, and (ii) Phenanthroline derivatives targeting telomerases to disrupt trypanosome DNA synthesis. Our thesis research evaluated the trypanocidal power of different molecules from these two families both by in vitro tests and in a mouse model infected with a strain of Trypanosoma brucei brucei. The purpose of this work was to identify new drug candidates. The results obtained have made it possible to identify compounds of interest that open up new pathways of research to control this parasite, as well as all kinetoplastidae.
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Submitted on : Friday, July 3, 2020 - 10:10:36 AM
Last modification on : Wednesday, October 5, 2022 - 4:01:48 AM


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  • HAL Id : tel-02885898, version 2



Clotilde Boudot. Recherche de nouvelles molécules trypanocides. Médecine humaine et pathologie. Université de Limoges, 2019. Français. ⟨NNT : 2019LIMO0078⟩. ⟨tel-02885898v2⟩



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