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

Wang, Jia; Wang, Chaolei; Wu, Zheng; Li, Xinnan; Xu, Shengtao; Liu, Jie; Lan, Qinying; Zhu, Zheying; Xu, Jinyi

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.

Citation

Wang, J., Wang, C., Wu, Z., Li, X., Xu, S., Liu, J., …Xu, J. (2018). Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II). Chemical Biology and Drug Design, 91(3), 756-762. https://doi.org/10.1111/cbdd.13136

• Journal Article Type: Article
• Acceptance Date: Oct 14, 2017
• Online Publication Date: Nov 7, 2017
• Publication Date: Feb 21, 2018
• Deposit Date: Oct 26, 2017
• Publicly Available Date: Nov 8, 2018
• Journal: Chemical Biology and Drug Design
• Print ISSN: 1747-0277
• Electronic ISSN: 1747-0285
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 91
• Issue: 3
• Pages: 756-762
• DOI: https://doi.org/10.1111/cbdd.13136
• Keywords: Alzheimer’s disease, acetylcholinesterase inhibitors, 4-isochromanone skeleton, benzyl pyridine
• Public URL: https://nottingham-repository.worktribe.com/output/913293
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/cbdd.13136/abstract
• Additional Information: This is the pre-peer reviewed version of the following article: Wang J, Wang C, Wu Z, et al. Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II). Chem Biol Drug Des. 2018;91:756–762, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/cbdd.13136/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Oct 26, 2017