924895-91-0Relevant academic research and scientific papers
Preparation and study of new poly-8-hydroxyquinoline chelators for an anti-alzheimer strategy
Deraeve, Celine,Boldron, Christophe,Maraval, Alexandrine,Mazarguil, Honore,Gornitzka, Heinz,Vendier, Laure,Pitie, Marguerite,Meunier, Bernard
, p. 682 - 696 (2008)
Fourteen different ligands have been synthesized with two covalently linked 8-hydroxyquinoline motifs that favor metal complexation. These bis-chelators include different bridges at the C2 positions and different substituents to modulate their physicochemical properties. They can form metal complexes in a ratio of one ligand per metal ion with CuII and ZnII, two metal ions involved in the formation of amyloid aggregates of the toxic Aβ-peptides in the Alzheimer disease. The apparent affinity of all bis-8-hydroxyquinoline ligands for CuII and ZnII are similar with logKCuII, ≈16 and logKZnII≈13 and are 10000 times more efficient than for the corresponding 8-hydroxyquinoline monomers. Their strong chelating capacities allow them to inhibit more efficiently than the corresponding monomers the precipitation of Aβ-peptides induced by CuII and ZnII and also to inhibit the toxic formation of H2O2 due to copper complexes of Aβ. The best results were obtained with a one-atom linker between the two quinoline units. X-ray analyses of single-crystals of Cu II, ZnII or NiII complexes of 2,2′-(2,2-propanediyl)-bis(8-hydroxyquinoline), including a oneatom linker, showed that all heteroatoms of the bis-8-hydroxyquinoline ligand chelate the same metal ion in a distorted square-planar geometry. The CuII and ZnII complexes include a fifth axial ligand and are pentacoordinated.
NOVEL POLYQUINOLINE DERIVATIVES AND THERAPEUTIC USE THEREOF
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Page/Page column 27, (2009/09/25)
The invention relates to compounds of general formula (I), to the process for the preparation thereof and to the use thereof as a therapeutic agent.
