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Synthèse et étude de nouveaux analogues de l’acadésine pour circonvenir les résistances dans les hémopathies malignes

Abstract : The fight against cancer is certainly one of the biggest challenges of the 21st century. Resistance that comes up against targeted therapy agents presents a particularly important aspect of this issue. The thesis presented here takes part within that framework. It aims at developing bioactive molecules able to circumvent resistance that have emerged against the treatment of certain hematological malignancies: chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS). Having developed a one-pot synthesis methodology that converts azides into 5-alkynyl-1,2,3-triazole, we synthesized two series of products: nucleosidic and non-nucleosidic. For each of these series, structure-activity relationships have been established. After running several cycles of optimization, three lead compounds particularly active on resistant cell lines of CML and MDS were selected. Further, their mode of action proved to be very interesting. It is based (partially or fully, depending on the compound) on a cellular process, which is experiencing a real renewed interest, the autophagy. An in vivo evaluation confirmed the promising activity of our nucleosidic lead compound. Moreover, studies aiming at determining the intracellular localization and molecular targets of our products are currently in progress
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https://tel.archives-ouvertes.fr/tel-02003542
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  • HAL Id : tel-02003542, version 1

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Hela Amdouni. Synthèse et étude de nouveaux analogues de l’acadésine pour circonvenir les résistances dans les hémopathies malignes. Autre. Université Côte d'Azur, 2016. Français. ⟨NNT : 2016AZUR4065⟩. ⟨tel-02003542⟩

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