Synthesis of a novel series of bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

Abstract

Nine potential AChE reactivators were synthesized using a modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by insecticide chlorpyrifos was tested in vitro. 2,2′-Bis(hydroxyiminomethyl)-1,1′-(1,4-phenylenedimethyl)-bispyridinium dibromide seems to be the most potent AChE reactivator. The reactivation potency of these compounds depends on structural factors such as length of the linking chain between both pyridinium rings and position of the oxime moiety on the pyridinium ring.

Keywords::

• Acetylcholinesterase
• reactivation
• pesticide
• chlorpyrifos
• reactivator
• oxime
• inhibition
• AChE

Acknowledgements

The authors express their appreciation to Mrs. M. Hrabinova for her technical assistance. The study was supported by a grant from the Ministry of Defense No. ONVLAJEP 20031 and by a grant from the Grant Agency of Charles University No. 302/2005/B-CH/FaF.