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 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 Cu-II, 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.