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BioMed Research International
Volume 2015 (2015), Article ID 965987, 9 pages
http://dx.doi.org/10.1155/2015/965987
Research Article

An Expedient Synthesis, Acetylcholinesterase Inhibitory Activity, and Molecular Modeling Study of Highly Functionalized Hexahydro-1,6-naphthyridines

1Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
2School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
3School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
4Pharmacogenetic and Novel Therapeutic Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Penang, Malaysia

Received 17 November 2014; Revised 9 January 2015; Accepted 9 January 2015

Academic Editor: Miroslav Pohanka

Copyright © 2015 Abdulrahman I. Almansour et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A series of hexahydro-1,6-naphthyridines were synthesized in good yields by the reaction of 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones with cyanoacetamide in the presence of sodium ethoxide under simple mixing at ambient temperature for 6–10 minutes and were assayed for their acetylcholinesterase (AChE) inhibitory activity using colorimetric Ellman’s method. Compound 4e with methoxy substituent at ortho-position of the phenyl rings displayed the maximum inhibitory activity with IC50 value of 2.12 μM. Molecular modeling simulation of 4e was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) enzyme to disclose binding interaction and orientation of this molecule into the active site gorge of the receptor.