Preparation of Tetradentate Copper Chelators as Potential Anti‐Alzheimer Agents

The uncontrolled redox activity of metal ions, especially copper, in the brains of patients with Alzheimer's disease (AD) should be considered the origin of intense oxidative damage to neurons in the AD brain. To obtain low‐molecular‐weight copper chelators that act as tetradentate ligands, we...

Full description

Saved in:
Bibliographic Details
Published in:ChemMedChem 2018-04, Vol.13 (7), p.684-704
Main Authors: Zhang, Weixin, Huang, Daya, Huang, Meijie, Huang, Ju, Wang, Dean, Liu, Xingguo, Nguyen, Michel, Vendier, Laure, Mazères, Serge, Robert, Anne, Liu, Yan, Meunier, Bernard
Format: Article
Language:English
Subjects:
Alzheimer's disease
Brain
Brain damage
Chelating agents
Chelation
Chemical Sciences
Coordination chemistry
Copper
Copper compounds
copper ligands
Homeostasis
Ligands
metal homeostasis
Metal ions
Metals
Neurodegenerative diseases
Oxidative stress
reactive oxygen species
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The uncontrolled redox activity of metal ions, especially copper, in the brains of patients with Alzheimer's disease (AD) should be considered the origin of intense oxidative damage to neurons in the AD brain. To obtain low‐molecular‐weight copper chelators that act as tetradentate ligands, we designed new compounds based on an 8‐aminoquinoline motif with a lateral chain attached at the 2‐position of the aromatic ring. Some of these new ligands, termed TDMQ for TetraDentate MonoQuinolines, are specific for copper chelation. Full characterization of these ligands is reported, as well as their affinities for CuII, and their capacities to inhibit oxidative stress induced by copper–amyloids activated by a reductant. Such metal ligands can be considered as potential anti‐AD agents, as they should be able to regulate the homeostasis of copper in brain tissue. Regulating copper homeostasis for AD: New tetradendate ligands (TDMQ) based on 8‐aminoquinoline were found to be specific chelators of copper(II) ions and are able to extract Cu2+ from toxic copper‐loaded amyloids. These ligands can transfer copper ions to physiological copper acceptors. They should be considered as potential regulators of copper homeostasis for Alzheimer's disease (AD) therapy.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.201700734