Donepezil Derivatives Targeting Amyloid-β Cascade in Alzheimer's Disease

doi:10.2174/1567205016666190228122956
摘要

阿尔茨海默氏病（AD）是一种神经退行性疾病，对社会的影响越来越大。由于目前可用的疗法仅具有短期作用，因此，利用AD病理生理学各个方面的知识，每年都会开发出大量新型化合物。为了更好地解决AD的病理复杂性，药物化学家最广泛采用的策略之一是基于多目标定向配体（MTDL）。多奈哌齐是目前公认的用于AD治疗的药物之一，可作为乙酰胆碱酯酶抑制剂。在这篇综述中，我们进行了广泛的文献调查，重点研究了多奈哌齐衍生的MTDL杂种，主要针对不同水平的胆碱酯酶和淀粉样β（Aβ）肽。靶向作用包括化合物与Aβ的直接相互作用，AChE诱导的Aβ聚集，BACE-1酶的抑制和生物金属平衡的调节，从而阻碍Aβ的组装。
关键词: 乙酰胆碱酯酶，阿尔茨海默氏病，淀粉样β蛋白，生物金属，β-分泌酶1，丁酰胆碱酯酶，多靶标定向配体，神经保护作用。
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DOI https://dx.doi.org/10.2174/1567205016666190228122956	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828
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