Cited by 31Cholinesterase and Neurodegenerative DiseasesSynthesis and biological activityEnzyme function and inhibition

Design, synthesis and biological evaluation of coumarin derivatives as novel acetylcholinesterase inhibitors that attenuate H2O2-induced apoptosis in SH-SY5Y cells

Yao, Dahong, Wang, Jing, Wang, Guan, Jiang, Yingnan, Shang, Lei, Zhao, Yuqian, Huang, Jian, Yang, Shilin +2 more·2016·Bioorganic Chemistry

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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Crossref · 10.1016/j.bioorg.2016.07.013

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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
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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