title: 9H-Carbazole Derivatives Containing the N-Benzyl-1,2,3-triazole Moiety as New Acetylcholinesterase Inhibitors.
abstract: A series of triazole-containing carbazole derivatives were designed as new anti-acetylcholinesterase (AChE) agents. The target compounds 6a-q were simply prepared via a one-pot three-component click reaction of N-propargyl-9H-carbazole, sodium azide, and an appropriate benzyl halide. The in vitro anti-cholinesterase assay showed that the unsubstituted benzyl derivative 6p along with the 2-F, 2-Me, 3-Me, 3-MeO, and 3-F analogs (6a, 6c, and 6g-i) had significant anti-AChE activity (IC50s ≤ 3.8 μM). Among them, the 2-methylbenzyl derivative 6c with an IC50 value of 1.9 μM was the most active compound. The SAR studies revealed that small halogen atoms such as the fluorine atom or electron-donating groups such as methyl or methoxy at the ortho or meta positions of the benzyl pendent group could be tolerated or improved the anti-AChE activity.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Chemistry, College of Science, Yazd University, Yazd, Iran.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Akrami
authors.forename: Bibi F
authors.initials: BF
authors.lastname: Mirjalili
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoobi
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Vosooghi
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D001665:Binding Sites; D002227:Carbazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D007700:Kinetics; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002227:Carbazoles; D002800:Cholinesterase Inhibitors; D008024:Ligands; D014230:Triazoles; D000110:Acetylcholinesterase
keywords: 9H-Carbazole; Acetylcholinesterase; Alzheimer's disease; Click chemistry; Docking study; Triazole