title: Benzofuran-derived benzylpyridinium bromides as potent acetylcholinesterase inhibitors.
abstract: A series of benzofuran-based N-benzylpyridinium derivatives 5a-o were designed and synthesized as novel AChE inhibitors. The synthetic pathway of the compounds involved the preparation of 4-(benzofuran-2-yl)pyridine intermediates via the reaction of different salicylaldehyde derivatives and 4-(bromomethyl)pyridine, followed by intramolecular cyclization. Subsequently, the 4-(benzofuran-2-yl)pyridines were N-benzylated by using appropriate benzyl bromide to afford the final product 5a-o. The results of in vitro AChE activity evaluation of synthesized compounds revealed that all compound had potent anti-AChE activity comparable or more potent than standard drug donepezil. The N-(3,5-dimethylbenzyl) derivative 5e with IC50 value of 4.1 nM was the most active compound, being 7-fold more potent than donepezil.
authors: Department of Chemistry, Faculty of Chemistry, Islamic Azad University, Yazd, Iran.
authors: Farzaneh
authors: F
authors: Baharloo
authors: Department of Chemistry, Faculty of Chemistry, Islamic Azad University, Yazd, Iran.
authors: Mohammad Hossein
authors: MH
authors: Moslemin
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors: Hamid
authors: H
authors: Nadri
authors: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medicinal Sciences, Kerman, Iran.
authors: Ali
authors: A
authors: Asadipour
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran, Iran.
authors: Mohammad
authors: M
authors: Mahdavi
authors: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Saeed
authors: S
authors: Emami
authors: Drug Design & Development Research Center, Tehran University of Medicinal Sciences, Tehran, Iran.
authors: Loghman
authors: L
authors: Firoozpour
authors: Department of Chemistry, Faculty of Chemistry, Islamic Azad University, Yazd, Iran.
authors: Razieh
authors: R
authors: Mohebat
authors: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran, Iran.
authors: Abbas
authors: A
authors: Shafiee
authors: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medicinal Sciences, Kerman, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medicinal Sciences, Tehran, Iran. Electronic address: aforoumadi@yahoo.com.
authors: Alireza
authors: A
authors: Foroumadi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D002800:Cholinesterase Inhibitors; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Benzofuran; Docking study; Pyridinium