Design, synthesis and molecular modeling of isothiochromanone derivatives as acetylcholinesterase inhibitors

Shuai, Wen; Li, Wenlong; Yin, Ying; Yang, Limei; Xu, Feijie; Xu, Shengtao; Yao, Hequan; Zhu, Zheying; Xu, Jinyi

Abstract

A series of novel isothio- and isoselenochromanone derivatives bearing N-benzyl pyridinium moiety were designed, synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. Results: Most of the target compounds exhibited potent anti-AChE activities with IC50 values in nanomolar ranges. Among them, compound 15a exhibited the most potent anti-AChE activity (IC50 = 2.7 nM), moderate antioxidant activity and low neurotoxicity. Moreover, the kinetic and docking studies revealed that compound 15a was a mixed-type inhibitor, which bounds to peripheral anionic site and catalytic active site of AChE. Conclusion: Those results suggested that compound 15a might be a potential candidate for AD treatment.

Citation

Shuai, W., Li, W., Yin, Y., Yang, L., Xu, F., Xu, S., …Xu, J. (2019). Design, synthesis and molecular modeling of isothiochromanone derivatives as acetylcholinesterase inhibitors. Future Medicinal Chemistry, 11(20), 2687-2699. https://doi.org/10.4155/fmc-2019-0125

• Journal Article Type: Article
• Acceptance Date: Aug 6, 2019
• Online Publication Date: Oct 9, 2019
• Publication Date: 2019-10
• Deposit Date: Nov 25, 2019
• Publicly Available Date: Oct 10, 2020
• Journal: Future Medicinal Chemistry
• Print ISSN: 1756-8919
• Electronic ISSN: 1756-8927
• Publisher: Future Science
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 20
• Pages: 2687-2699
• DOI: https://doi.org/10.4155/fmc-2019-0125
• Keywords: • Acetylcholinesterase inhibitor; Alzheimer's disease; Dual binding site; isoselenochromanone; isothiochromanone
• Public URL: https://nottingham-repository.worktribe.com/output/3407041
• Publisher URL: https://www.future-science.com/doi/10.4155/fmc-2019-0125