title: Phthalimide-Derived N-Benzylpyridinium Halides Targeting Cholinesterases: Synthesis and Bioactivity of New Potential Anti-Alzheimer's Disease Agents.
abstract: In order to develop potent dual-binding cholinesterase inhibitors as potential drugs for the treatment of Alzheimer's disease, we designed and synthesized phthalimide-based acetylcholinesterase (AChE) inhibitors (7) containing a substituted N-benzylpyridinium residue. The in vitro anti-cholinesterase assay employing the target compounds against AChE and butyrylcholinesterase (BChE) revealed the 2-fluorobenzylpyridinium derivative 7d as the most potent compound against both enzymes, with IC50 values of 0.77 and 8.71 μM. The docking study of compound 7d into the active site of AChE showed the gorge-spanning binding mode, in which the compound spans the narrow hydrophobic gorge from the bottom to the rim.
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 Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maedeh
authors.initials: M
authors.lastname: Golipoor
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: Faculty of Pharmacy, Department of Medicinal Chemistry, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Faculty of Pharmacy, Department of Medicinal Chemistry, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.affiliation: Faculty of Pharmacy, Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D006736:Horses; D062105:Molecular Docking Simulation; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014101:Torpedo
chemical_list: D002800:Cholinesterase Inhibitors; D010797:Phthalimides; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: 1,3-Dioxoisoindoline; Acetylcholinesterase; Alzheimer's disease; Phthalimide; Pyridinium