title: Potent acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and docking study of acridone linked to 1,2,3-triazole derivatives.
abstract: A novel series of acridone linked to 1,2,3-triazole derivatives have been synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. The synthetic approach was started from the reaction of 2-bromobenzoic acid with aniline derivatives and subsequent cyclization reaction to give acridone derivatives. Then, reaction of the later compounds with propargyl bromide followed by azide-alkyne cycloaddition reaction (click reaction) led to the formation of the title compounds in good yields. Among the synthesized compounds, 10-((1-(4-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methoxyacridin-9(10H)-one 9g, depicted the most potent anti-AChE activity (IC50 = 7.31 μM). Also, docking study confirmed the results obtained through in vitro experiments and predicted possible binding conformation.
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Maryam
authors: M
authors: Mohammadi-Khanaposhtani
authors: Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mina
authors: M
authors: Saeedi
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Narges Shamsaei
authors: NS
authors: Zafarghandi
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Mohammad
authors: M
authors: Mahdavi
authors: Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Reyhaneh
authors: R
authors: Sabourian
authors: Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Elahe Karimpour
authors: EK
authors: Razkenari
authors: Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.
authors: Heshmatollah
authors: H
authors: Alinezhad
authors: Department of Pharmacognosy, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Mahnaz
authors: M
authors: Khanavi
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Alireza
authors: A
authors: Foroumadi
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors: Abbas
authors: A
authors: Shafiee
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14176, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: akbarzad@tums.ac.ir.
authors: Tahmineh
authors: T
authors: Akbarzadeh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054831:Acridones; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009033:Culicidae; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004593:Electrophorus; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000166:Acridines; D054831:Acridones; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D014230:Triazoles; C041300:acridone; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Acridone-1,2,3-triazole; Alzheimer's disease; Docking study