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Synthesis of a novel series of non-symmetrical bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase
Authors:Kamil Musilek  Ondrej Holas  Kamil Kuca  Daniel Jun  Vlastimil Dohnal  Martin Dolezal
Affiliation:1. Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic;2. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05, Hradec Kralove, Czech Republic;3. Centre of Advanced Studies, Faculty of Military Health Sciences, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic;4. Department of Food Technology, Mendel University of Agriculture and Forestry Brno, Zemedelska 1, 613 00, Brno, Czech Republic
Abstract:Nine potential non-symmetrical xylene-bridged AChE reactivators were synthesized using modifications of currently known synthetic pathways. Their potency to reactivate AChE inhibited by the nerve agent tabun and the insecticide paraoxon together with nine symmetrical xylene-bridged compounds, was tested in vitro. Seven compounds were promising against paraoxon-inhibited AChE. Two compounds were found to be more potent against tabun-inhibited AChE than obidoxime at a concentration applicable in vivo.
Keywords:acetylcholinesterase  reactivation  nerve agent  tabun  pesticide  paraoxon  oxime
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