title: Design, synthesis, biological evaluation and docking study of 5-oxo-4,5-dihydropyrano[3,2-c]chromene derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors.
abstract: A series of fused coumarins namely 5-oxo-4,5-dihydropyrano[3,2-c]chromenes linked to N-benzylpyridinium scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The 1-(4-fluorobenzyl)pyridinium derivative 6g showed the most potent anti-AChE activity (IC50 value=0.038 μM) and the highest AChE/BuChE selectivity (SI>48). The docking study permitted us to rationalize the observed structure-affinity relationships and to detect possible binding modes.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoobi
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Alipour
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sakhteman
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghandi
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000378:metabolism*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D008954:Models, Biological; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Chromenes; Coumarins; Docking study