Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (partⅡ)

Wang, Jia and Wang, Chaolei and Wu, Zheng and Li, Xinnan and Xu, Shengtao and Liu, Jie and Lan, Qinying and Zhu, Zheying and Xu, Jinyi (2017) Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (partⅡ). Bioorganic & Medicinal Chemistry Letters, 25 (22). 5212–5216. ISSN 1464-3405

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Abstract

A series of novel 4-isochromanone compounds bearing N-benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti-AChE activity with an IC50 value of 0.15 nM and high AChE/BuChE selectivity (SI >5000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti-Alzheimer’s disease agents.

Item Type: Article
Keywords: Alzheimer’s disease, acetylcholinesterase inhibitors, 4-isochromanone skeleton, benzyl pyridine
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1016/j.bmcl.2015.09.063
Depositing User: Zhu, Zheying
Date Deposited: 26 Oct 2017 08:56
Last Modified: 16 Nov 2017 17:50
URI: http://eprints.nottingham.ac.uk/id/eprint/47573

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