Discovery of Novel Non-Oxime Reactivators Showing In Vivo Antidotal Efficiency for Sarin Poisoned Mice

Molecules. 2022 Feb 7;27(3):1096. doi: 10.3390/molecules27031096.

Abstract

A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imidazole to the ortho position of phenols would dramatically enhance reactivation efficiency. Moreover, the in vivo experiment was conducted, and the results demonstrated that Mannich phenol L10R1 (30 mg/kg, ip) could afford 100% 48 h survival for mice of 2*LD50 sarin exposure, which is promising for the development of non-oxime reactivators with central efficiency.

Keywords: Mannich phenol; acetylcholinesterase; non-oximes; organophosphate; reactivators.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Antidotes / pharmacology*
  • Chemical Warfare Agents / toxicity
  • Cholinesterase Reactivators / pharmacology*
  • Humans
  • Mice
  • Neurotoxicity Syndromes / drug therapy*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology
  • Oximes
  • Pyridinium Compounds / pharmacology*
  • Sarin / toxicity*

Substances

  • Antidotes
  • Chemical Warfare Agents
  • Cholinesterase Reactivators
  • Oximes
  • Pyridinium Compounds
  • Sarin
  • Acetylcholinesterase