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

摘要

A series of hexahydro-l, -naphthyridines were synthesized in good yields by the reaction of 3, -bis[(.E)-arylmethylidene] tetrahydro-4(lH)-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 IC_(50) value of 2.12μM. 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.