Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease

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• 作者：Jacques Joubert^a ; ^{jjoubert@uwc.ac.za} ; Germaine B. Foka^a ; Benjamin P. Repsold^b ; Douglas W. Oliver^b ; Erika Kapp^a ; Sarel F. Malan^a
• 关键词：Alzheimer's disease ; Coumarin ; Donepezil ; MAO-B ; Cholinesterase ; Molecular modeling
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：853-864
• 全文大小：1637 K
• 卷排序：125

文摘

Twenty-five 7-substituted coumarin derivatives were successfully synthesised and evaluated. Compound 3 showed potent and selective MAO-B and BuChE inhibitory activity. Compound 19 was able to inhibit MAO-B, AChE and BuChE in the μm range. Docking revealed that 19 binds simultaneously to the CAS and PAS sites of AChE. It is suggested that 19 will be able to inhibit AChE induced Aβ aggregation.