Design, synthesis and biological evaluation of coumarin derivatives as novel acetylcholinesterase inhibitors that attenuate H2O2-induced apoptosis in SH-SY5Y cells
Abstract
A novel series of coumarin derivatives were designed, synthesized and investigated for inhibition of cholinesterase, including acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE). This biological study showed that these compounds containing piperazine ring had significant inhibition activities on AChE rather than BuChE. Further study suggested that 9x, as one of this kind of structure derivative, showed the strongest inhibition activity on AChE with an IC50 value of 34nM. Moreover, molecular docking, flow cytometry (FCM), and western blot assay suggested that 9x could induce cytoprotective autophagy to attenuate H2O2-induced cell death in human neuroblastoma SH-SY5Y cells. These findings highlight a new approach for the development of a novel potential neuroprotective compound targeting AChE with autophagy-inducing activity in future Alzheimer's disease (AD) therapy.
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In vitro models with neurons isolated from the CNS and/or immortalized cell lines demonstrated that H2O2 causes cell death through apoptosis.
“Various in vitro models carried out with neurons isolated from the CNS and/or with immortalized cell lines, demonstrated that H2O2 causes cell death through apoptosis [118,131,132,133,134,135].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [134]
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- Authors
- Yao, D., Wang, J., Wang, G., Jiang, Y., Shang, L., Zhao, Y., Huang, J., Yang, S., Wang, J., & Yu, Y.
- Affiliations
- Shenyang Pharmaceutical University (CN)
- China Medical University (CN)
- Taishan Medical University (CN)
- Corresponding author
- Yang, Shilin
- Wang, Jinhui
- Yu, Yamei
- ORCID
- Venue
- Bioorganic Chemistry
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 68
- Pages
- 112-123
- ISSN
- 0045-2068 (ISSN-L)
- OpenAlex
- W2478249342
- Cited by
- 30
- References
- 28
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 3
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Fund (81303270, U1303124, 81202403, 81573290)
- Liaoning Science and Technology Project (2013226027-4)
- Jilin Science and Technology Progress Project (20130204058YY)
- Applied Basic Research Project of Sichuan Science and Technology Department (2013JY0154)
- Shenyang Pharmaceutical University Scientific Research Fund (ZCJJ2013407)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Keywords
- coumarins, acetylcholinesterase inhibitors, butyrylcholinesterase, piperazine, H2O2-induced apoptosis, autophagy, neuroprotection, SH-SY5Y cells, Alzheimer's disease, molecular docking, structure-activity relationship
- MeSH terms
- Acetylcholinesterase, Cholinesterase Inhibitors, Coumarins, Dose-Response Relationship, Drug, Humans, Hydrogen Peroxide, Structure-Activity Relationship, Drug Design, Molecular Structure, Apoptosis, Cell Line, Tumor
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