title: Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives.
abstract: A series of 7-hydroxycoumarin derivatives connected by an amidic linker to the different amines were designed and synthesized as cholinesterase inhibitors. Most compounds showed remarkable inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among them, N-(1-benzylpiperidin-4-yl)acetamide derivative 4r with IC50 value of 1.6 μM was the most potent compound against AChE. The selectivity index of compound 4r for anti-AChE activity was about 26. Moreover, the compound 4r significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. The docking study of compound 4r with AChE enzyme showed that both CAS and PAS are occupied by the ligand.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Alipour
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoobi
authors.affiliation: Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.affiliation: Neurobiomedical Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Farshad
authors.initials: F
authors.lastname: Homayouni Moghadam
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Hasanpour
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran. Electronic address: ashafiee@ams.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004593:Electrophorus; D006736:Horses; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship; D014468:Umbelliferones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Coumarins; Docking study