Skip to Main content Skip to Navigation

Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action

Abstract : Leishmaniasis is a neglected tropical disease for which the current therapeutic arsenal is limited. This work aimed at finding new therapeutic drugs by targeting the Leishmania cell wall. Lipophosphoglycan (LPG) is the major glycoconjugate in promastigotes cell wall, consisting of a hexasaccharide core including a galactofuranose motif. Galactofuranose is absent in mammalian membranes, thus could be a therapeutic target. First, this work studied the galactofuranosyl-transferases involved in the metabolism of this furanose, as well as a mutase, also necessary for the metabolism of galactofuranose. Once targets were identified in the two parasitic stages, galactofuranose derivatives were tested for antileishmanial activity on promastigotes and amastigotes forms of Leishmania donovani. A compound showed interesting results and has been studied further, the n-octyl-galactofuranose (Galf). Different techniques have been used to characterize its mode of action on promastigotes and amastigotes: electron paramagnetic resonance, transmission electron microscopy, nuclear magnetic resonance or flow cytometry. Infected macrophages treated with Galf were able to produce oxygen derivatives species, leading us to look at the immunomodulatory capacity of Galf derivatives. Thus, the last part of this work focused on the study of macrophage polarization by galactofuranosides on an in vitro model of human macrophages. We were able to show that Galf stimulates macrophages towards M1 polarization, which could explain the decreased growth of amastigotes inside macrophage cells.
Document type :
Complete list of metadatas

Cited literature [277 references]  Display  Hide  Download
Contributor : Abes Star :  Contact
Submitted on : Thursday, December 19, 2019 - 11:01:20 AM
Last modification on : Wednesday, September 9, 2020 - 5:35:39 AM
Long-term archiving on: : Friday, March 20, 2020 - 2:40:25 PM


Version validated by the jury (STAR)


  • HAL Id : tel-02418898, version 1


Sorya Belaz. Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action. Médecine humaine et pathologie. Université Rennes 1, 2017. Français. ⟨NNT : 2017REN1B044⟩. ⟨tel-02418898⟩



Record views


Files downloads