Development of new acetylcholinesterase reactivators: molecular modeling versus in vitro data.
In this work a theoretical methodology for evaluation of the association and kinetic reactivation constants of oximes using the Molegro and Spartan softwares was proposed and validated facing in vitro data previously reported in the literature. Results showed a very good agreement between the theoretical binding free energies of the reactivators and experimental data, suggesting that the proposed methodology could work well in the prediction of kinetic and thermodynamics parameters for oximes that might be helpful for the design and selection of new and more effective oximes.
Ramalho
Teodorico C
TC
Chemistry Department, Federal University of Lavras, Lavras, MG, Brazil. teo@dqi.ufla.br
França
Tanos C C
TC
Rennó
Magdalena N
MN
Guimarães
Ana P
AP
da Cunha
Elaine F F
EF
Kuca
Kamil
K
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000378:metabolism / Q000494:pharmacology*; D055808:Drug Discovery / Q000379:methods*; D004789:Enzyme Activation / Q000187:drug effects*; D051379:Mice; D008958:Models, Molecular; D010755:Organophosphates / Q000494:pharmacology; D010091:Oximes / Q000378:metabolism / Q000494:pharmacology; D011789:Quantum Theory; D013816:Thermodynamics
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D000110:Acetylcholinesterase; C009374:tabun