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

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 poss...

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Main Authors: Wang, Jia, Wang, Chaolei, Wu, Zheng, Li, Xinnan, Xu, Shengtao, Liu, Jie, Lan, Qinying, Zhu, Zheying, Xu, Jinyi
Format: Article
Language:English
Published: Wiley 2018
Subjects:
Online Access:https://eprints.nottingham.ac.uk/47573/
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author Wang, Jia
Wang, Chaolei
Wu, Zheng
Li, Xinnan
Xu, Shengtao
Liu, Jie
Lan, Qinying
Zhu, Zheying
Xu, Jinyi
author_facet Wang, Jia
Wang, Chaolei
Wu, Zheng
Li, Xinnan
Xu, Shengtao
Liu, Jie
Lan, Qinying
Zhu, Zheying
Xu, Jinyi
author_sort Wang, Jia
building Nottingham Research Data Repository
collection Online Access
description 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.
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publishDate 2018
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spelling nottingham-475732018-11-07T04:30:11Z https://eprints.nottingham.ac.uk/47573/ 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 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. Wiley 2018-02-21 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/47573/1/CBDD%202017-accepted.pdf Wang, Jia, Wang, Chaolei, Wu, Zheng, Li, Xinnan, Xu, Shengtao, Liu, Jie, Lan, Qinying, 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 Alzheimer’s disease acetylcholinesterase inhibitors 4-isochromanone skeleton benzyl pyridine http://onlinelibrary.wiley.com/doi/10.1111/cbdd.13136/abstract doi:10.1111/cbdd.13136 doi:10.1111/cbdd.13136
spellingShingle Alzheimer’s disease
acetylcholinesterase inhibitors
4-isochromanone skeleton
benzyl pyridine
Wang, Jia
Wang, Chaolei
Wu, Zheng
Li, Xinnan
Xu, Shengtao
Liu, Jie
Lan, Qinying
Zhu, Zheying
Xu, Jinyi
Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II)
title Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II)
title_full Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II)
title_fullStr Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II)
title_full_unstemmed Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II)
title_short Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II)
title_sort design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing n-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part ii)
topic Alzheimer’s disease
acetylcholinesterase inhibitors
4-isochromanone skeleton
benzyl pyridine
url https://eprints.nottingham.ac.uk/47573/
https://eprints.nottingham.ac.uk/47573/
https://eprints.nottingham.ac.uk/47573/