Synthesis and characterization of 8-aminoquinolines, substituted by electron donating groups, as high-affinity copper chelators for the treatment of Alzheimer's disease - 08/06/19

Doi : 10.1016/j.crci.2019.05.003

Ju Huang ^a,^b , Michel Nguyen ^b , Yan Liu ^a,^⁎ , Anne Robert ^b,^⁎ , Bernard Meunier ^a,^b
^a Guangdong University of Technology (GDUT), School of Chemical Engineering and Light Industry, Number 100 Waihuan Xi Road, Education Mega Center, Guangzhou, PR China
^b Laboratoire de chimie de coordination du CNRS (LCC-CNRS), 205, route de Narbonne, BP 44099, 31077 Toulouse cedex 4, France

^∗Corresponding author.^∗∗Corresponding author.

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Abstract

The deregulation of copper homeostasis generates copper–amyloid aggregation and strongly participates in neuron damage in the brains of patients with Alzheimer's disease. Therefore, copper chelators able to regulate copper homeostasis should be considered as potential therapeutic agents. On the basis of a bidentate amine side chain attached at the 2-position of an 8-aminoquinoline motif, a series of low-molecular-weight copper chelators have been designed to act as specific tetradentate Cu(II) chelators. The affinity of these ligands for Cu(II) and their selectivity for Cu(II) with respect to Zn(II) are reported. These ligands provide a square planar tetradentate coordination sphere that should be suitable to extract copper (II) from copper–amyloid complexes, and are therefore expected to regulate copper homeostasis in vivo.

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