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.
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.
Musilek
Kamil
K
Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. musilek@pmfhk.cz
Holas
Ondrej
O
Kuca
Kamil
K
Jun
Daniel
D
Dohnal
Vlastimil
V
Dolezal
Martin
M
D000110:Acetylcholinesterase / Q000737:chemistry*; D002619:Chemical Warfare Agents / Q000737:chemistry; D002621:Chemistry / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D015195:Drug Design; D008956:Models, Chemical; D009768:Obidoxime Chloride / Q000737:chemistry; D010755:Organophosphates / Q000737:chemistry*; D010261:Paraoxon / Q000737:chemistry*; D010575:Pesticides / Q000737:chemistry; D011726:Pyridinium Compounds / Q000737:chemistry*; D012492:Salts / Q000737:chemistry; D014992:Xylenes / Q000737:chemistry*
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D010575:Pesticides; D011726:Pyridinium Compounds; D012492:Salts; D014992:Xylenes; D009768:Obidoxime Chloride; D000110:Acetylcholinesterase; D010261:Paraoxon; C009374:tabun