MMSL 2014, 83(4):165-177 | DOI: 10.31482/mmsl.2014.027

CHEMICAL WARFARE: PERSPECTIVES ON REACTIVATING THE ENZYME ACETYLCHOLINESTERASE INHIBITED BY ORGANOPHOSPHATESOriginal article

Juliana de O. S. Giacoppo1, Willian E. A. de Lima1, Kamil Kuča ORCID...2,3, Elaine F. F. da Cunha1, Tanos C. C. França2,4*, Teodorico de C. Ramalho1,2
1 Chemistry department, Federal University of Lavras, CP 3037, Lavras, MG, 37200-000, Brazil
2 Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralové, Rokitanského 62, 500 03 Hradec Kralové III, Czech Republic
3 Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
4 Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense (LMCBD), Military Institute of Engineering, Rio de Janeiro/RJ, 22290-270, Brazil

It is known that nerve agents are potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of the neurotransmitter acetylcholine and, thus, transmission of nerve impulses. The process of AChE inhibition by nerve agents can be reversed by a nucleophile able to dephosphorylate the enzyme. In this sense, oximes exhibit this characteristic and are able to remove the neurotoxic and reactivate AChE. Here, we review experimental and theoretical results involving docking and quantum mechanical-molecular mechanics hybrid methods (QM/MM), using Molegro® and Spartan® softwares to analyze the interaction of different nerve agents and oximes with AChE and to evaluate kinetic constants of reactivation.

Keywords: Chemical warfare; organophosphates; oximes; docking; QM/MM

Received: May 17, 2014; Revised: November 3, 2014; Published: December 5, 2014  Show citation

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de Giacoppo, J.O.S., de Lima, W.E.A., Kuča, K., da Cunha, E.F.F., França, T.C.C., & de Ramalho, T.C. (2014). CHEMICAL WARFARE: PERSPECTIVES ON REACTIVATING THE ENZYME ACETYLCHOLINESTERASE INHIBITED BY ORGANOPHOSPHATES. MMSL, 83(4), 165-177. doi: 10.31482/mmsl.2014.027
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