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., Yao, H., Zhu, Z., & 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