Molecules 2012, 17(10), 12072-12085; doi:10.3390/molecules171012072
Article

A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles

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,* email and Jorge Trilleras 4,* email
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.
Received: 23 July 2012; in revised form: 30 August 2012 / Accepted: 17 September 2012 / Published: 15 October 2012
(This article belongs to the Section Medicinal Chemistry)
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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 7g is located on the periphery of the AChE active site.
Keywords: Knoevenagel condensation; acrylonitriles; AChE inhibitors; docking; ligand-protein interactions; selectivity

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Cite This Article

MDPI and ACS Style

Torre, P.; 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.

AMA Style

Torre P, Saavedra LA, Caballero J, Quiroga J, Alzate-Morales JH, Cabrera MG, 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(10):12072-12085.

Chicago/Turabian Style

Torre, Pedro ; Saavedra, Luis A.; Caballero, Julio; Quiroga, Jairo; Alzate-Morales, Jans H.; Cabrera, Margarita G.; Trilleras, Jorge. 2012. "A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles." Molecules 17, no. 10: 12072-12085.

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