Synthesis of the novel series of bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against chlorpyrifos-inhibited acetylcholinesterase

Bioorg Med Chem Lett. 2006 Feb;16(3):622-7. doi: 10.1016/j.bmcl.2005.10.059. Epub 2005 Nov 8.

Abstract

Six potential AChE reactivators were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by insecticide chlorpyrifos was tested in vitro. According to the results, (E)-1-(2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide seems to be the most potent AChE reactivator. The reactivation potency of these compounds depends on structural factors such as constitution of the linking chain between both pyridinium rings, position of the oxime moiety at the pyridinium ring and presence of quaternary nitrogens.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Chlorpyrifos / pharmacology*
  • Cholinesterase Inhibitors / pharmacology*
  • Cholinesterase Reactivators / pharmacology*
  • Dose-Response Relationship, Drug
  • Hydrocarbons, Brominated / chemical synthesis
  • Hydrocarbons, Brominated / pharmacology*
  • Nitrogen / chemistry
  • Oximes / chemistry
  • Pyridinium Compounds / chemical synthesis
  • Pyridinium Compounds / pharmacology*
  • Rats

Substances

  • (E)-1-(2-hydroxyiminomethylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide
  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • Hydrocarbons, Brominated
  • Oximes
  • Pyridinium Compounds
  • Acetylcholinesterase
  • Chlorpyrifos
  • Nitrogen