Multitarget-Directed Benzylideneindanone Derivatives: Anti-尾-Amyloid (A尾) Aggregation, Antioxidant, Metal Chelation, and Monoamine Oxidase B (MAO-B) Inhibition Properties against Alzheimer鈥檚 Disease

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• 作者：Ling Huang ; Chuanjun Lu ; Yang Sun ; Fei Mao ; Zonghua Luo ; Tao Su ; Huailei Jiang ; Wenjun Shan ; Xingshu Li
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：October 11, 2012
• 年：2012
• 卷：55
• 期：19
• 页码：8483-8492
• 全文大小：487K
• 年卷期：v.55,no.19(October 11, 2012)
• ISSN：1520-4804

文摘

A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer鈥檚 disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced 尾-amyloid (A尾_1鈥?2) aggregation (10.5鈥?0.1%, 20 渭M) and MAO-B activity (IC₅₀ of 7.5鈥?0.5 渭M), to act as potential antioxidants (ORAC-FL value of 2.75鈥?.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit A尾_1鈥?2 aggregation (80.1%), and MAO-B (IC₅₀ = 7.5 渭M) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced A尾_1鈥?2 aggregation and disassembling the well-structured A尾 fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.