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

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

Acknowledgements

The authors express their appreciation to Mrs M. Hrabinova for her technical assistance. The work was supported by a grant from the Grant Agency of Charles University No. 302/2005/B-CH/FaF and by a grant from the Ministry of Defence of Czech Republic No. FVZ0000501.