Nguyen Michel, Robert Anne, Sournia-Saquet Alix, Vendier Laure, Meunier Bernard
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, BP 44099, 31077 Toulouse cedex 4 (France).
Chemistry. 2014 May 26;20(22):6771-85. doi: 10.1002/chem.201402143. Epub 2014 May 5.
The non-controlled redox-active metal ions, especially copper, in the brain of patients with Alzheimer disease (AD) should be considered at the origin of the intense oxidative damage in the AD brain. Several bis(8-aminoquinoline) ligands, such as 1 and PA1637, are able to chelate Cu(2+) with high affinity, and are specific chelators of copper with respect to iron and zinc. They are able to efficiently extract Cu(2+) from a metal-loaded amyloid. In addition, these tetradentate ligands are specific for the chelation of Cu(2+) compared with Cu(+). Consequently, the copper ion is easily released from the bis(8-aminoquinoline) ligand under reductive conditions, and can be trapped again by a protein having some affinity for copper such as human serum albumin (HSA) proteins. In addition, the copper is not efficiently released from [Cu(CQ)2] in reductive conditions. The catalytic production of H2O2 by [Cu(2+)-Aβ(1-28)]/ascorbate is inhibited in vitro by the bis(8-aminoquinoline) 1, suggesting that 1 should be able to play a protective role against oxidative damages induced by copper-loaded amyloids.
阿尔茨海默病（AD）患者大脑中不受控制的氧化还原活性金属离子，尤其是铜离子，应被视为AD大脑中强烈氧化损伤的根源。几种双（8-氨基喹啉）配体，如1和PA1637，能够以高亲和力螯合Cu(2+)，并且相对于铁和锌而言是铜的特异性螯合剂。它们能够从负载金属的淀粉样蛋白中有效提取Cu(2+)。此外，与Cu(+)相比，这些四齿配体对Cu(2+)的螯合具有特异性。因此，在还原条件下，铜离子很容易从双（8-氨基喹啉）配体中释放出来，并可再次被对铜具有一定亲和力的蛋白质（如人血清白蛋白（HSA）蛋白）捕获。此外，在还原条件下，铜不能有效地从[Cu(CQ)2]中释放出来。双（8-氨基喹啉）1在体外抑制了[Cu(2+)-Aβ(1-28)]/抗坏血酸催化生成H2O2，这表明1应该能够对由负载铜的淀粉样蛋白诱导的氧化损伤起到保护作用。
