Novel Nucleophilic Compounds with Oxime Group as Reactivators of Paraoxon-Inhibited Cholinesterases

Title: Novel Nucleophilic Compounds with Oxime Group as Reactivators of Paraoxon-Inhibited Cholinesterases

Volume: 7 Issue: 4

Author(s): Lucie Musilova, Daniel Jun, Jiri Palecek, Vladimir Cirkva, Kamil Musilek, Martin Paar, Martina Hrabinova, Miroslav Pohanka and Kamil Kuca

Affiliation:

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Nerve agent, Pesticide, Reactivator, Oxime, Paraoxon, Scavenger

Abstract: New cholinesterase reactivators are synthesized as potential antidotes for treatment of organophosphorus agent poisonings or as part of pseudo catalytic scavengers for improvement of the nerve agent prophylaxis. In this study, three novel potential cholinesterase reactivators (K064 - (E)-1-(pyridinium)-4-(2-hydroxyiminomethylpyridinium)-but-2-ene dibromide; K065-(E)-1-(quinolinium)-4-(2-hydroxyiminomethylpyridinium)-but-2-ene dibromide; K066-(E)-1- (isoquinolinium)-4-(2-hydroxyiminomethylpyridinium)-but-2-ene dibromide) were synthesized and tested for their potency to reactivate acetylcholinesterase (AChE, EC 3.1.1.3) and butyrylcholinesterase (BChE, 3.1.1.8) inhibited by pesticide paraoxon. As resulted, none from the synthesized compounds surpassed currently clinically used reactivators (pralidoxime, obidoxime and HI-6).

Cite this article as:

Musilova Lucie, Jun Daniel, Palecek Jiri, Cirkva Vladimir, Musilek Kamil, Paar Martin, Hrabinova Martina, Pohanka Miroslav and Kuca Kamil, Novel Nucleophilic Compounds with Oxime Group as Reactivators of Paraoxon-Inhibited Cholinesterases, Letters in Drug Design & Discovery 2010; 7 (4) . https://dx.doi.org/10.2174/157018010790945823