High specificity is a key parameter for copper ligands as future therapeutic agents for Alzheimer’s, Wilson’s, and cancer diseases

The loss of copper homeostasis is considered a characteristic feature of several major human diseases such as Alzheimer’s, Wilson’s, or cancer diseases. Consequently, the design of new efficient ligands targeting copper regulation is a major concern of therapeutic bioinorganic chemistry and should take in consideration the chelator structures for being copper-specific and the redox properties of the corresponding complexes to obtain suitable pharmacological activities. As an improvement of previously developed amine ligands, N4-tetradentate 8-aminoquinoline chelators, are able to inhibit memory and behavior impairment in Alzheimer mice, by generating square planar Cu(II) complexes suitable for the efficient extraction of copper ions from metallated amyloid peptides, leading to a reduction of the neurotoxic oxidative stress in the brain. These chelators also reverse the hepatotoxic accumulation of copper in animals with Wilson’s disease and inhibit the proliferation and migration of human cancer cell lines. This review summarizes the gradual and logical development of twenty-five years of research in our group on copper-specific chelators and their promising development as potential therapeutic tools against diseases in which copper is involved.