Multitarget-Directed Benzylideneindanone Derivatives: Anti-β-Amyloid (Aβ) Aggregation, Antioxidant, Metal Chelation, and Monoamine Oxidase B (MAO-B) Inhibition Properties against Alzheimer's Disease
Multitarget-Directed Benzylideneindanone Derivatives: Anti-β-Amyloid (Aβ) Aggregation, Antioxidant, Metal Chelation, and Monoamine Oxidase B (MAO-B) Inhibition Properties against Alzheimer's Disease
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DOI：
10.1021/jm300978h
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发表时间：
2012-10-11
影响因子：
7.3
通讯作者：
Li, Xingshu
中科院分区：
文献类型：
--
作者：
Huang, Ling;Lu, Chuanjun;Li, Xingshu
设计、合成并评价了一系列新的苯亚甲基茚满酮衍生物作为抗阿尔茨海默病的多靶点配体。体外研究表明，大多数分子表现出显著的抑制自身诱导的β-淀粉样蛋白（A β（1-42））聚集（10.5- 80.1%，20 μ M）和MAO-B活性（IC 50为7.5-40.5 μ M）的能力，作为潜在的抗氧化剂（ORAC-FL值为2.75-9.37），并作为金属螯合剂发挥作用。特别地，化合物41具有最大的抑制A β（1-42）聚集的能力（80.1%），并且MAO-B（IC 50 = 7.5 μ M）也是优异的抗氧化剂和金属螯合剂。此外，它能够抑制Cu（II）诱导的A β（1-42）聚集并分解结构良好的A β原纤维。这些结果表明，化合物41是一种优良的治疗AD的多功能药物。
A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced beta-amyloid (A beta(1-42)) aggregation (10.5-80.1%, 20 mu M) and MAO-B activity (IC50 of 7.5-40.5 mu M), to act as potential antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit A beta(1-42) aggregation (80.1%), and MAO-B (IC50 = 7.5 mu M) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced A beta(1-42) aggregation and disassembling the well-structured A beta fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.