Synthesis of asymmetrical bispyridinium compounds bearing cyano-moiety and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase

Three asymmetrical AChE reactivators with cyano-moiety and propane linker were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by nerve agent tabun and insecticide paraoxon was tested in vitro and compared to pralidoxime, HI-6, obidoxime, K027, and K048. According to the results, three compounds seem to be promising against paraoxon-inhibited AChE. Better results were obtained for bisquaternary substances at least with one oxime group in position four. None of tested substances was able to satisfactorily reactivate tabun-inhibited AChE at concentration applicable for in vivo experiments.

Graphical abstractA series of asymmetrical bisquaternary reactivators of acetylcholinesterase (AChE) bearing cyano-moiety with propane connecting chain was synthesized and evaluated on tabun and paraoxon-inhibited AChE with promising results.Figure optionsDownload full-size imageDownload as PowerPoint slide