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 and Wang, Chaolei and Wu, Zheng and Li, Xinnan and Xu, Shengtao and Liu, Jie and Lan, Qinying and Zhu, Zheying and Xu, Jinyi (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). pp. 756-762. ISSN 1747-0277

[img] PDF - Repository staff only until 7 November 2018. - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (989kB)

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
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.
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: https://doi.org/10.1111/cbdd.13136
Depositing User: Zhu, Zheying
Date Deposited: 26 Oct 2017 08:56
Last Modified: 01 Apr 2018 13:16
URI: http://eprints.nottingham.ac.uk/id/eprint/47573

Actions (Archive Staff Only)

Edit View Edit View