Development of promising oximes against nerve agent and/or pesticide intoxication

Issue title: Sensing and Destroying Chemical Weapons and Pesticides Based on the Symposium at the 238th American Chemical Society Meeting Washington DC, USA, August 18–19, 2009

Article type: Research Article

Authors: Musilek, Kamil^; | Holas, Ondrej | Komloova, Marketa | Zdarova-Karasova, Jana | Pohanka, Miroslav | Kuca, Kamil^;

Affiliations: Faculty of Military Health Sciences, Department of Toxicology, Trebesska, Hradec Kralove, Czech Republic | Faculty of Pharmacy in Hradec Kralove, Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Heyrovskeho, Hradec Kralove, Czech Republic | Faculty of Military Health Sciences, Center of Advanced Studies, Trebesska, Hradec Kralove, Czech Republic | Faculty of Science, Department of Chemistry, University of Jan Evangelista Purkyne, Usti nad Labem, Czech Republic

Note: [] Corresponding author: Kamil Musilek, Tel.: +420 973 251 523; Fax: +420 495 518 094; E-mail: musilek@pmfhk.cz, kamil.musilek@gmail.com

Abstract: Acetylcholinesterase (AChE) reactivators are crucial antidotes for the treatment of organophosphate (OP) intoxication. Since pralidoxime, there is still no AChE reactivator able to counteract the full spectrum of different organophosphorus compounds. Our effort has been concerned on development of novel AChE reactivators against tabun and OP pesticides. Hundreds of novel AChE reactivators were prepared. Several novel compounds were found to be potent reactivators both in vitro and in vivo. One compound (K203) was highlighted against tabun poisoning and one compound (K027) was highlighted against OP pesticide poisoning. Selected compounds are becoming promising candidates for replacement of former clinically used AChE reactivators.

Keywords: Acetylcholinesterase, reactivation, oxime, nerve agent, pesticide

DOI: 10.3233/MGC-2010-0023

Journal: Main Group Chemistry, vol. 9, no. 3-4, pp. 355-361, 2010