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Dérivés de flavonoïdes et de vérapamil comme ligands des transporteurs MRP1 et ABCG2 : de la conception à l'activité anticancéreuse

Abstract : Resistance to chemotherapeutic agents (Multidrug Resistance or MDR) is characterized by the overexpression of membrane ABC proteins, such as MRP1 and ABCG2. These transporters decrease intracellular concentrations of chemotherapeutic agents by increasing their efflux from the cancer cell. In order to find effective modulators of drug resistance, we have designed, synthesized and investigated MRP1 activators and ABCG2 inhibitors. We designed and synthesized new derivatives of flavonoids and verapamil as activators of MRP1. These activators are capable of inducing a rapid and massive efflux of intracellular glutathione via MRP1 and causing cells death by apoptosis. We have also designed and synthesized new compounds, derivatives of chromone, as selective inhibitors of ABCG2, to restore sensitivity of cancer cells to chemotherapeutic agents. The biological evaluation of investigated compounds enabled us to identify new activators of MRP1 as well as potent and selective inhibitors of ABCG2. Keywords: MRP1, ABCG2, flavonoids, verapamil analogs, chromone, inhibitors, activators
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Submitted on : Monday, May 30, 2011 - 3:38:17 PM
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Estelle Genoux. Dérivés de flavonoïdes et de vérapamil comme ligands des transporteurs MRP1 et ABCG2 : de la conception à l'activité anticancéreuse. Biochimie [q-bio.BM]. Université de Grenoble, 2011. Français. ⟨NNT : 2011GRENV015⟩. ⟨tel-00596929⟩

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