title: The Necessity of Having a Tetradentate Ligand to Extract Copper(II) Ions from Amyloids.
abstract: The accumulation of redox-active metal ions, in particular copper, in amyloid plaques is considered to the cause of the intensive oxidation damage to the brain of patients with Alzheimers disease (AD). Drug candidates based on a bis(8-aminoquinoline) tetradentate ligand are able to efficiently extract Cu(2+) from copper-loaded amyloids (Cu-Aβ). Contrarily, in the presence of a bidentate hydroxyquinoline, such as clioquinol, the copper is not released from Aβ, but remains sequestrated within a Aβ-Cu-clioquinol ternary complex that has been characterized by mass spectrometry. Facile extraction of copper(II) at a low amyloid/ligand ratio is essential for the re-introduction of copper in regular metal circulation in the brain. As, upon reduction, the Cu(+) is easily released from the bis(8-aminoquinoline) ligand unable to accommodate Cu(I), it should be taken by proteins with an affinity for copper. So, the tetradentate bis(8-aminoquinoline) described here might act as a regulator of copper homeostasis.
authors: Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique (CNRS) 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France).
authors: Michel
authors: M
authors: Nguyen
authors: Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique (CNRS) 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France).
authors: Lionel
authors: L
authors: Rechignat
authors: Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique (CNRS) 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France).
authors: Anne
authors: A
authors: Robert
authors: Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique (CNRS) 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France) ; Department of Chemical Engineering, Guangdong University of Technology, Education Mega Center 100 Waihuan Xi Rd, Guangzhou (P. R. China).
authors: Bernard
authors: B
authors: Meunier
keywords: Alzheimers disease; chelating agents; copper homeostasis; medicinal chemistry; therapeutic agents