Multitarget drug design strategy against Alzheimer’s disease: Homoisoflavonoid Mannich base derivatives serve as acetylcholinesterase and monoamine oxidase B dual inhibitors with multifunctional properties

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• 作者：Yan Li^a ; Xiaoming Qiang^a ; Li Luo^a ; Xia Yang^a ; Ganyuan Xiao^a ; Yunxiaozhu Zheng^a ; Zhongcheng Cao^a ; Zhipei Sang^b ; Fu Su^a ; ^{sufu@scu.edu.cn} ; Yong Deng^a ; ^{dengyong@scu.edu.cn}
• 关键词：Alzheimer&rsquo ; s disease ; Homoisoflavonoid ; Mannich base derivatives ; Acetylcholinesterase inhibitors ; Monoamine oxidase B inhibitors ; Multifunctional properties
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：25
• 期：2
• 页码：714-726
• 全文大小：1325 K
• 卷排序：25

文摘

A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer’s disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC50 = 2.49 ± 0.08 nM and 1.74 ± 0.0581 μM, respectively), good self- and Cu2+-induced Aβ1-42 aggregation inhibitory potency, antioxidant activity, biometal chelating ability and high BBB permeability. These multifunctional properties make 10d as an excellent candidate for the development of efficient drugs against AD.