title: Synthesis of novel chromenones linked to 1,2,3-triazole ring system: Investigation of biological activities against Alzheimer's disease.
abstract: In this work, novel chromenones linked to 1,2,3-triazole ring system were synthesized and evaluated for their anti-ChE activity. Among them, N-((1-(2-chlorobenzyl)-1H-1,2,3-triazol-5-yl)methyl)-8-methoxy-2-oxo-2H-chromene-3-carboxamide (6m) showed good anti-acetylcholinesterase activity (IC50=15.42μM). Also, compound 6m demonstrated neuroprotective effect against H2O2-induced cell death in PC12 neurons, however, it showed no beta-secretase (BACE1) inhibitory activity. Docking and kinetic studies separately confirmed dual binding activity of compound 6m since it targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE.
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: Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran P.O. Box 3353-5111, Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Safavi
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: Drug Design and Research Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Edraki
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 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; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D014230:Triazoles; D000110:Acetylcholinesterase
keywords: 1,2,3-Triazole; Alzheimer’s disease; Anti-cholinesterase; Chromenones; Docking study; Neuroprotective activity; β-Secretase inhibitory activity