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Article Dans Une Revue European Journal of Inorganic Chemistry Année : 2017

Structures of the copper and zinc complexes of PBT2, a chelating agent evaluated as potential drug for neurodegenerative diseases

Résumé

Clioquinol and PBT2, based on a 8-hydroxyquinoline scaffold, have been proposed as drugs able to treat the disruption of metal homeostasis in neurodegenerative diseases, especially Alzheimer's disease (AD). They are believed to reduce metal–amyloid (Aβ) interactions and regulate redox homeostasis in AD brains. Therefore, the understanding of the molecular aspects of metal chelation by 8-hydroxyquinolines is clearly important for the development of future metal chelators as putative drugs. Despite this, literature data on these aspects are rather limited. We report herein the stoichiometries and structures of the copper(II) and zinc(II) complexes of PBT2. The reported data indicate that the coordination chemistry of PBT2 is characterized by high versatility and a lack of metal selectivity. For each metal, several complexes can co-exist, and the copper complexes differ from their zinc analogues. The structures of the PBT2 complexes are significantly different to those reported for complexes of clioquinol, the prototype of this series. As PBT2 can be a bi- or tridentate ligand, different complexes can be formed with copper, including ternary complexes PBT2–Cu–X. The versatile structures of the metal complexes of PBT2 in vivo, especially in the brains of AD patients, should be dependent on competitive ligands, including amyloids. This feature might be a limitation for an efficient extraction of copper from amyloids.
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Dates et versions

hal-01940591 , version 1 (30-11-2018)

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Michel Nguyen, Laure Vendier, Jean-Luc Stigliani, B. Meunier, Anne Robert. Structures of the copper and zinc complexes of PBT2, a chelating agent evaluated as potential drug for neurodegenerative diseases. European Journal of Inorganic Chemistry, 2017, 3, pp.600-608. ⟨10.1002/ejic.201601120⟩. ⟨hal-01940591⟩
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