title: Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors.
abstract: A new series of tacrine-1,2,3-triazole hybrids were designed, synthesized, and evaluated as potent dual cholinesterase inhibitors. Most of synthesized compounds showed good in vitro inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 7-chloro-N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5l) was found to be the most potent anti-AChE derivative (IC50= 0.521 μM) and N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5j) demonstrated the best anti-BChE activity (IC50= 0.055 μM). In vivo studies of compound 5l in Morris water maze task confirmed memory improvement in scopolamine-induced impairment. Also, molecular modeling and kinetic studies showed that compounds 5l and 5j bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CS) of the AChE and BChE.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Najafi
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Saeedi
authors.affiliation: Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Karimpour-Razkenari
authors.affiliation: Department of Biology, Science and Research Branch Islamic Azad, Tehran, Iran.
authors.forename: Raymond
authors.initials: R
authors.lastname: Asatouri
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fahimeh
authors.initials: F
authors.lastname: Vafadarnejad
authors.affiliation: Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors.forename: Farshad Homayouni
authors.initials: FH
authors.lastname: Moghadam
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Khanavi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: msharifzadeh@tums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: akbarzad@tums.ac.ir.
authors.forename: Tahmineh
authors.initials: T
authors.lastname: Akbarzadeh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000201:enzymology; D062105:Molecular Docking Simulation; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D014230:Triazoles; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Alzheimer's disease; Cholinesterase; Docking study; Dual binding; Morris water maze; Tacrine-1,2,3-triazole