Design,synthesis and biological evaluation of coumarin derivatives as novel acetylcholinesterase inhibitors that attenuate H2O2-induced apoptosis in SH-SY5Y cells |
| |
| Institution: | 1. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China;2. Department of Neurology, Liaocheng People’s Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng 252000, China;3. School of Pharmacy, China Medical University, Shenyang 110122, China;4. Department of Emergency Radiology, Liaocheng People’s Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng 252000, China;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;2. Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO Box 2476, Melbourne 3001, Australia;3. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;1. Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand;2. Laboratory of Natural Products, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand;3. Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand;1. Anadolu University, Faculty of Pharmacy, Department of Pharmacology, Eskişehir, Turkey;2. Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Eskişehir, Turkey;1. Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, 9 Medyczna Str., 30-688, Kraków, Poland;2. Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, 9 Medyczna Str., 30-688, Kraków, Poland;3. Department of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, 9 Medyczna Str., 30-688, Kraków, Poland;4. Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, 9 Medyczna Str., 30-688, Kraków, Poland;5. Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, 9 Medyczna Str., 30-688, Kraków, Poland;6. Institute of Psychiatry and Neurology, 9 Sobieskiego Str., 02-957, Warsaw, Poland;7. Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000, Ljubljana, Slovenia;1. Department of Gerontology, Shanghai Sixth People''s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 200233, China;2. Department of Cardiology, Shanghai Sixth People''s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 200233, China;1. Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China;2. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 30071, PR China |
| |
| 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 34 nM. 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
