title: An expedient synthesis, acetylcholinesterase inhibitory activity, and molecular modeling study of highly functionalized hexahydro-1,6-naphthyridines.
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.
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulrahman I
authors.initials: AI
authors.lastname: Almansour
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Raju Suresh
authors.initials: RS
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Arumugam
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
authors.forename: Alireza
authors.initials: A
authors.lastname: Basiri
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Kia
authors.affiliation: Pharmacogenetic and Novel Therapeutic Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800 Penang, Malaysia.
authors.forename: Mohamed Ashraf
authors.initials: MA
authors.lastname: Ali
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D003198:Computer Simulation; D004789:Enzyme Activation; D008956:Models, Chemical; D008958:Models, Molecular; D009287:Naphthyridines / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D002800:Cholinesterase Inhibitors; D009287:Naphthyridines; D000110:Acetylcholinesterase