Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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In vitro Screening of Oxime Reactivators on the Model of Paraoxon-inhibited Acetylcholinesterase-SAR Study

  • Holas, Ondrej (Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague) ;
  • Musilek, Kamil (Department of Toxicology, Faculty of Military Health Sciences) ;
  • Pohanka, Miroslav (Center of Advanced Studies, Faculty of Military Health Sciences) ;
  • Kuca, Kamil (Center of Advanced Studies, Faculty of Military Health Sciences) ;
  • Opletalova, Veronika (Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague) ;
  • Jung, Young-Sik (Bioorganic Science Division, Korea Research Institute of Chemical Technology)
  • Received : 2010.01.13
  • Accepted : 2010.04.12
  • Published : 2010.06.20
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Abstract

Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Standard in vitro test was chosen using a rat brain homogenate as the source of AChE. Screening of reactivation potency was performed with two concentration of reactivator (1000 ${\mu}M$ and 10 ${\mu}M$). Results were compared to established reactivators pralidoxime, methoxime, HI-6, trimedoxime and obidoxime. More than 30 novel reactivators performed equal or better reactivation ability of POX-inhibited AChE compared to currently used reactivators. The structure-activity relationship for reactivators of paraoxon-inhibited AChE was developed.

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