| Literature DB >> 28011206 |
Ganyuan Xiao1, Yan Li1, Xiaoming Qiang1, Rui Xu1, Yunxiaozhu Zheng1, Zhongcheng Cao1, Li Luo1, Xia Yang1, Zhipei Sang2, Fu Su3, Yong Deng4.
Abstract
A series of 4'-aminochalcone-revastigmine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. The results showed that most of these compounds exhibited good multifunctional activities. In particular, compound 6c displayed the best inhibitory potency on acetylcholinesterase (IC50=4.91μM), and significant antioxidative activity with a value 2.83-fold of Trolox. The kinetic analysis of AChE inhibition revealed that 6c showed mixed-type inhibition, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. In addition, 6c inhibited self-induced Aβ1-42 aggregation and Cu2+-induced Aβ1-42 aggregation by 89.5% and 79.7% at 25μM respectively, as well as acted as a selective monoamine oxidase B inhibitor (IC50=0.29μM) and a selective biometal chelator. Furthermore, 6c could cross the blood-brain barrier in vitro. Based on these results, Compound 6c could be considered as a very promising lead compound for Alzheimer's disease.Entities:
Keywords: Acetylcholinesterase inhibitors; Alzheimer’s disease; Aβ aggregation inhibitors; Chalcone carbamate derivatives; Monoamine oxidase B inhibitors; Multifunctional agents
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Year: 2016 PMID： 28011206 DOI： 10.1016/j.bmc.2016.12.013
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641