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Synthèse de composés aromatiques, anticancéreux potentiels, modulateurs des voies de signalisation de l'apoptose

Abstract : Apoptosis or programmed cell death is a genetically and complex process required for normal development. It is involved in maintenance of tissue homeostasis and removal of damaged or infected cells. Proteins of the Bcl-2 (B-cell lymphoma) family play a critical role in the regulation of apoptosis. Based on their function, these proteins can be divided into two groups : pro-apoptotic and anti-apoptotic members. Protein-protein interactions determine life-or-death of a cell by controlling the release of mitochondrial apoptogenic factors. Anti-apoptotic proteins are overexpressed in many human cancers and often associated with resistance to conventional forms of therapies. So, there is a considerable need to develop agents that specifically target these proteins in order to restore apoptosis in tumours. We were interested in the preparation of quinoline trimers which could inhibit anti-apoptotic proteins of the Bcl-2 family. In the first part of this manuscript, members of the Bcl-2 protein family are described as well as inhibitors of anti-apoptotic proteins. The second part of this work develops the synthesis of our quinolein derivatives. The key step is a Suzuki cross-coupling, involving preparation of various diversely substituted monomers. Biological evaluation of these new compounds is in progress.
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  • HAL Id : tel-00725076, version 1

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Sidonie Broch. Synthèse de composés aromatiques, anticancéreux potentiels, modulateurs des voies de signalisation de l'apoptose. Chimie organique. Université Blaise Pascal - Clermont-Ferrand II, 2009. Français. ⟨NNT : 2009CLF21970⟩. ⟨tel-00725076⟩

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