title: Docking and quantum mechanic studies on cholinesterases and their inhibitors.
abstract: Docking studies and density functional theory (DFT) calculations were made for 88 N-aryl derivatives and for some acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) residues. Based on this information, some compounds were synthesized and tested kinetically in vitro as AChE inhibitors. Finally, some chemical properties of the N-aryl derivatives were calculated: partition coefficient (pi) and molecular electrostatic potentials (MESPs) whereas their electronic effects (rho) were taken from the literature. The results showed that all compounds act inside the AChE gorge, making pi-pi interactions and hydrogen bonds with Trp86 and Ser203 and by high HOMO energies of Ser2003 and high LUMO energies of N-aryl derivatives. These theoretical calculations for AChE are in agreement with the experimental data, whereas such calculations for BChE do not show the same behavior which could be due to in spite of both cholinesterase enzymes displaying similar functional activities they do possess important structural differences at their catalystic sites.
authors.affiliation: Sección de Graduados y Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, DF, Mexico. jcorreab@ipn.mx <jcorreab@ipn.mx>
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.forename: Cesar
authors.initials: C
authors.lastname: Flores-Sandoval
authors.forename: Jesús
authors.initials: J
authors.lastname: Marín-Cruz
authors.forename: Arturo
authors.initials: A
authors.lastname: Rojo-Domínguez
authors.forename: L Michel
authors.initials: LM
authors.lastname: Espinoza-Fonseca
authors.forename: José G
authors.initials: JG
authors.lastname: Trujillo-Ferrara
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D011789:Quantum Theory
chemical_list: D000577:Amides; D002800:Cholinesterase Inhibitors; D007094:Imides; D008024:Ligands; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase