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Complexes osmium nitrosyle avec des ligands bioactifs : synthèse, structure, réactivité et activité antiproliférative in vitro

Abstract : The PhD thesis was dedicated to the synthesis and bio-physic-chemical characterization of osmium nitrosyl complexes which could release nitric oxide (NO) in tumor cells to combine the anticancer properties of the platinum group complexes and the nitric oxide cytotoxicity. The first chapter presents the state of the art in the field of anticancer compounds and the role of nitric oxide in the apoptosis. The second chapter concerns the synthesis and characterization of azole complexes with the general formulae (C)[Os(NO)Cl4(A)] (C = Bu4N+, Na+, HA+; A = indazole, pyrazole, benzimidazole, imidazole), where the most cytotoxic is H2ind[cis-Os(NO)Cl4(indazole)]. The third chapter focuses on the kinetic and thermodynamic study of the trans ↔ cis isomerisation of (Bu4N)[Os(NO)Cl4(indazole)] complex by NMR, which highlights a dissociative isomerisation process. The fourth chapter concerns the synthesis and the characterization of amino acids complexes with the general formulae (Bu4N)[Os(NO)Cl4(L)] (L = gly, picolinate, L-, D-pro) of whose antiproliferative activity is very low. The last chapter is dedicated to the synthesis and characterization of heterometallic clusters with the general formulae [{Os(NO)Cl3(Ox)}4Ln] (Ln = Gd, Tb, Dy, Y ; Ox = oxalate), where the coordination number 8 or 9 depends on its ionic radius. The precursor {Os(NO)Cl3(Ox)} has the highest antiproliferative activity among of all osmium nitrosyl known so far
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Submitted on : Tuesday, November 12, 2013 - 4:32:16 PM
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Anatolie Gavriluta. Complexes osmium nitrosyle avec des ligands bioactifs : synthèse, structure, réactivité et activité antiproliférative in vitro. Autre. Université Claude Bernard - Lyon I, 2013. Français. ⟨NNT : 2013LYO10147⟩. ⟨tel-00903651⟩

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