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首页> 外文期刊>Coordination chemistry reviews >Recent progress in multifunctional metal chelators as potential drugs for Alzheimer's disease
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Recent progress in multifunctional metal chelators as potential drugs for Alzheimer's disease

机译：多功能金属螯合剂作为阿尔茨海默氏病潜在药物的最新进展

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Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative illness, which involves the progressive deterioration of intellectual functions and behavioral disorders. Several therapeutic approaches have been proposed, but only four acetylcholinesterase inhibitors and one N-methyl-D-aspartate receptor antagonist have been approved by the US Food and Drug Administration, which have quite limited effectiveness and that mostly provide palliative therapy. The complex pathology of this multifaceted disease and the possible interconnections among numerous intervening factors have led to the development of several multi-target candidate drugs. This review describes the most recent progress in multifunctional. compounds containing a biometal (Fe, Cu, Zn) chelating unity for potential AD prevention/therapy. The importance of including a chelating moiety in these anti-AD drug candidates is associated with the recognized roles played by metal dyshomeostasis and related oxidative stress in AD pathogenesis, particularly by preceding or inducing the hallmark pathologies of this disease (neurofibrillary tangles, senile plaques, and reactive oxygen species). This review focuses on recent approaches based on the combination or fusion of different functions in a unique molecular entity, including chelating moieties, with various types of donor atoms and denticity in several scaffolds, i.e., 8-hydroxyquinolines, beta-aminopyridines and other diamino-based chelators, phenol-amino derivatives, amino/hydroxyl chalcones, 3-hydroxy-4-pyridinones, flavonoids, and hydroxyanthraquinones. (C) 2016 Elsevier B.V. All rights reserved.
机译：阿尔茨海默氏病（AD）是一种慢性不可逆的神经退行性疾病，涉及智力功能和行为障碍的逐步恶化。已经提出了几种治疗方法，但是美国食品和药物管理局仅批准了四种乙酰胆碱酯酶抑制剂和一种N-甲基-D-天冬氨酸受体拮抗剂，它们的疗效相当有限，并且大多数提供姑息治疗。这种多方面疾病的复杂病理学以及众多干预因素之间可能的相互联系，导致了几种多靶点候选药物的开发。这篇评论描述了多功能方面的最新进展。含有生物金属（铁，铜，锌）螯合剂的化合物，可用于潜在的AD预防/治疗。在这些抗AD候选药物中包括螯合部分的重要性与金属异常增加和相关的氧化应激在AD发病机理中发挥的公认作用有关，特别是通过提前或诱发该疾病的标志性病理（神经原纤维缠结，老年斑，和活性氧）。这篇综述着重于基于独特分子实体中不同功能的组合或融合的最新方法，这些分子包括螯合部分，几种类型的供体原子和几种支架中的密度，即8-羟基喹啉，β-氨基吡啶和其他二氨基-螯合剂，酚氨基衍生物，氨基/羟基查耳酮，3-羟基-4-吡啶酮，类黄酮和羟基蒽醌。 （C）2016 Elsevier B.V.保留所有权利。

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