A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles
by
Pedro De la Torre 1,2, Luis Astudillo Saavedra 1, 
Julio Caballero 2, Jairo Quiroga 3, Jans H. Alzate-Morales 2, Margarita Gutiérrez Cabrera 1,* and Jorge Trilleras 4,*
Julio Caballero 2, Jairo Quiroga 3, Jans H. Alzate-Morales 2, Margarita Gutiérrez Cabrera 1,* and Jorge Trilleras 4,*
1
Laboratorio Síntesis Orgánica, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, 3460000, Chile
2
Centro de Bioinformática y Simulación Molecular, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, 3460000, Chile
3
Grupo de Investigación de Compuestos Heterocíclicos, Department of Chemistry, Universidad del Valle A. A. 25360 Cali, Colombia
4
Grupo de Investigación en Compuestos Heterocíclicos, Programa de Química, Facultad de Ciencias Básicas, Universidad del Atlántico, Km 7 Antigua vía Puerto Colombia, A.A.1890, Barranquilla, Colombia
*
Authors to whom correspondence should be addressed.
Molecules 2012, 17(10), 12072-12085; https://doi.org/10.3390/molecules171012072
Received: 23 July 2012 / Revised: 30 August 2012 / Accepted: 17 September 2012 / Published: 15 October 2012
(This article belongs to the Section Medicinal Chemistry)
(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 7g is located on the periphery of the AChE active site.
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Keywords:
Knoevenagel condensation; acrylonitriles; AChE inhibitors; docking; ligand-protein interactions; selectivity
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This is an open access article distributed under the Creative Commons Attribution License
MDPI and ACS Style
Torre, P.D.; Saavedra, L.A.; Caballero, J.; Quiroga, J.; Alzate-Morales, J.H.; Cabrera, M.G.; Trilleras, J. A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles. Molecules 2012, 17, 12072-12085.
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