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Design, Synthesize and Bio-Evaluate 1,2-Dihydroisoquinolin-3(4H)-One Derivates as Acetylcholinesterase and β-Secretase Dual Inhibitors in Treatment with Alzheimer’s Disease
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作者 Youchao Deng yuren jiang +1 位作者 Xiongjie Zhao Jinlian Wang 《Journal of Biosciences and Medicines》 2016年第1期112-123,共12页
With the recent research advances in molecular biology and technology, many credible hypothe-ses about the progress of Alzheimer’s disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses a... With the recent research advances in molecular biology and technology, many credible hypothe-ses about the progress of Alzheimer’s disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are commonly used to develop reliable therapeutic agents. The multitarget-directed ligand (MTDL) approach was taken in this work to develop multi-functional agents, which can mainly serve as dual BACE 1 and AChE inhibitors. Depending on the scaffolds of (+)-(S)- dihydro-ar-tumerone and (-)-gallocatechin gallate, 3 series of new compounds have been designed, synthesized and evaluated, from which we have identified 2-(2-(3-methylbenzoyl)-3-oxo-1,2,3,4- tetrahydroisoquinolin-6-yl) isoindoline-1,3-dione (3d) as a new cholinesterase and β-secretase dual inhibitor without toxicity. Furthermore, 3d also exhibits hydrogen peroxide scavenging activity which could help to reduce the reactive oxygen species (ROS) in the brain of AD patients. 展开更多
关键词 β-Secretase (BACE 1) Acetylcholinesterase (AChE) Inhibitor Alzheimer’s Disease (AD)
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