title: Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety.
abstract: A number of N-(2-(1H-indol-3-yl)ethyl)-2-oxo-2H-chromene-3-carboxamides were synthesized and tested against AChE and BuChE. The in vitro assessment of the synthesized compounds 4a-o revealed that most of them had significant activity toward AChE. The SAR study demonstrated that the introduction of benzyloxy moiety on the 7-position of coumarin scaffold can improve the anti-AChE activity. The best result was obtained with 7-(4-fluorobenzyl)oxy moiety in the case of compound 4o, displaying IC50 value of 0.16 μM. Based on the docking study of AChE, the prototype compound 4o was laid across the active site and occupied both peripheral anionic site (PAS) and catalytic anionic site (CAS).
authors.affiliation: Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Ghanei-Nasab
authors.affiliation: Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoobi
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
authors.affiliation: Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Marjani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
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 Medicinal Sciences, Tehran, 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 Medicinal Sciences, Tehran, Iran. Electronic address: shafieea@tums.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects*; D000818:Animals; D002091:Butyrylcholinesterase / Q000187:drug effects; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000737:chemistry
chemical_list: D002800:Cholinesterase Inhibitors; D003374:Coumarins; D014363:Tryptamines; C030820:tryptamine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Butyrylcholinesterase; Coumarin; Indole