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.

中文翻译：

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制备四齿铜螯合剂作为潜在的抗阿尔茨海默病药物

在阿尔茨海默氏病（AD）患者的大脑中，金属离子（尤其是铜）的不受控制的氧化还原活性应被认为是AD大脑神经元受到强烈氧化损伤的根源。为了获得充当四齿配体的低分子量铜螯合剂，我们基于8-氨基喹啉基序设计了一种新化合物，该基序在芳环的2位连接了侧链。这些新的配体中的某些，被称为TetraDentate MonoQuinolines的TDMQ，专门用于铜螯合。报告了这些配体的全面表征，以及它们对Cu ^II的亲和力以及它们抑制由还原剂激活的铜淀粉样蛋白诱导的氧化应激的能力。此类金属配体可被视为潜在的抗AD药物，因为它们应能够调节脑组织中铜的稳态。