title: Synthesis of bistetrahydroquinolines as potential anticholinesterasic agents by double Diels-Alder reactions.
abstract: The tetrahydroquinoline ring system is a unit found in many biologically active natural products and pharmacologically relevant therapeutic agents. A new series of bistetrahydroquinolines (bis-THQs) was synthesized using imino Diels-Alder reactions between dialdehydes, anilines and N-vinyl-2-pyrrolidone (NVP). The notable features of this procedure are mild reaction conditions, greater selectivity and good yields of products. In addition, the inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of some selected derivatives is reported. The feasible binding modes of these active compounds, within AChE and BuChE binding sites, were predicted by molecular docking experiments and their binding affinity was estimated by means of free energy calculations through the MM-GBSA approximation.
authors.affiliation: Laboratorio Síntesis Orgánica, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca 3460000, Chile. mgutierrez@utalca.cl.
authors.forename: Yorley
authors.initials: Y
authors.lastname: Duarte
authors.forename: Margarita
authors.initials: M
authors.lastname: Gutiérrez
authors.forename: Luis
authors.initials: L
authors.lastname: Astudillo
authors.forename: Jans
authors.initials: J
authors.lastname: Alzate-Morales
authors.forename: Natalia
authors.initials: N
authors.lastname: Valdés
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D061565:Cycloaddition Reaction; D055808:Drug Discovery; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D002800:Cholinesterase Inhibitors; D011804:Quinolines; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase