Structure-activity relationship for the reactivators of acetylcholinesterase inhibited by nerve agent VX

Med Chem. 2013 Aug;9(5):689-93. doi: 10.2174/1573406411309050008.

Abstract

Nerve agents such as sarin, VX and tabun are organophosphorus compounds able to inhibit an enzyme acetylcholinesterase (AChE). AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. None from the known AChE reactivators is able to reactivate AChE inhibited by all kinds of nerve agents. In this work, reactivation potency of seventeen structurally different AChE reactivators was tested in vitro and subsequently, relationship between their chemical structure and biological activity was outlined. VX was chosen as appropriate member of the nerve agent family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Molecular Structure
  • Organothiophosphorus Compounds / chemical synthesis
  • Organothiophosphorus Compounds / chemistry
  • Organothiophosphorus Compounds / pharmacology*
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Organothiophosphorus Compounds
  • VX
  • Acetylcholinesterase