title: A novel class of selective acetylcholinesterase inhibitors: synthesis and evaluation of (E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles.
abstract: (E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles are described as a new class of selective inhibitors of acetylcholinesterase (AChE). The most potent compound in the series exhibited good AChE inhibitory activity (IC₅₀ = 64 µM). Compound 7f was found to be more selective than galanthamine in inhibiting AChE and it showed a moderate selectivity index. Kinetic studies on AChE indicated that a competitive type of inhibition pattern exist for these acrylonitrile derivates. Molecular docking models of the ligand-AChE complexes suggest that compound 7 g is located on the periphery of the AChE active site.
authors.affiliation: Laboratorio Síntesis Orgánica, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca 3460000, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: de la Torre
authors.forename: Luis Astudillo
authors.initials: LA
authors.lastname: Saavedra
authors.forename: Julio
authors.initials: J
authors.lastname: Caballero
authors.forename: Jairo
authors.initials: J
authors.lastname: Quiroga
authors.forename: Jans H
authors.initials: JH
authors.lastname: Alzate-Morales
authors.forename: Margarita Gutiérrez
authors.initials: MG
authors.lastname: Cabrera
authors.forename: Jorge
authors.initials: J
authors.lastname: Trilleras
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000181:Acrylonitrile / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D000181:Acrylonitrile