title: 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.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Dahong
authors.initials: D
authors.lastname: Yao
authors.affiliation: Department of Neurology, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng 252000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yingnan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: yangshilin@suda.edu.cn.
authors.forename: Shilin
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: profwjh@126.com.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Emergency Radiology, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng 252000, China. Electronic address: yuyamei252000@163.com.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D003374:Coumarins; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase