title: SEARCH FOR POTENTIAL CHOLINESTERASE INHIBITORS FROM THE ZINC DATABASE BY VIRTUAL SCREENING METHOD.
abstract: A virtual screening of the ZINC database was applied for the identification of novel cholinesterase inhibitors. The first step allowed to select compounds with favorable physicochemical properties. Then, the compounds were screened with the pharmacophore models built using crystal structures of donepezil, tacrine, decamethonium and bis-7-tacrine with acetylcholinesterase and well characterized interactions of bis-nor-meptazinol with butyrylcholinesterase. The selected compounds from the group of donepezil were docked to acetyl-cholinesterase giving 7 structures for further studies. These compounds were tested against cholinesterases and two of them, 1-[4-(1H-indol-3-ylmethyl)piperazin-1-yl]-2-phenoxyethanone 2 and 2-[(1-benzylpiperidine-4- yl)amino]-1-phenylethanol 4 displayed, respectively, 50.1% and 79.5% of inhibition against butyryl- cholinesterase at the concentration of 100 µM.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.forename: Dawid
authors.initials: D
authors.lastname: Panek
authors.forename: Michalina
authors.initials: M
authors.lastname: Hebda
authors.forename: Anna
authors.initials: A
authors.lastname: Więckowska
authors.forename: Natalia
authors.initials: N
authors.lastname: Guzior
authors.forename: Barbara
authors.initials: B
authors.lastname: Malawska
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D001665:Binding Sites; D002091:Butyrylcholinesterase; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D016208:Databases, Factual; D015195:Drug Design; D062105:Molecular Docking Simulation
chemical_list: D002800:Cholinesterase Inhibitors; D002091:Butyrylcholinesterase