Synthesis and Pharmacological Evaluation of Novel Selenoethers Glycerol Derivatives for the Treatment of Pain and Inflammation: Involvement of Nitrergic and Glutamatergic Systems

Appl Biochem Biotechnol. 2019 Apr;187(4):1398-1423. doi: 10.1007/s12010-018-2887-z. Epub 2018 Sep 19.

Abstract

In the present study, the synthesis of new selenoethers from nucleophilic substitution reaction between organyl halides and nucleophilic species of selenium generated in situ was demonstrated. After, this method was applied for the synthesis of pyridylselenides glycerol derivatives 9b and 9c and the antinociceptive and anti-inflammatory effects, as well as, acute toxicity were evaluated. In the formalin test, the compound 9b caused a reduction in licking time in both phases. Compounds 9b and 9c increased the latency to response in the hot-plate test and reduced the licking time induced by glutamate. Our results revealed the involvement of the nitrergic and/or glutamatergic pathways in the antinociceptive action of the compounds. Additionally, 9b and 9c did not cause any toxicity signals and oxidative stress parameters were not modified by treatments. Here, it was developed an alternative and efficient method for the synthesis of selenoethers glycerol derivatives. Furthermore, we demonstrated that this class is indeed interesting for the research of new drugs. Graphical Abstract ᅟ.

Keywords: 3-Aminopyridil compounds; Glutamate; Glycerol; Nitric oxide; Nociception; Selenoether.

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Chemistry Techniques, Synthetic
  • Ethers / chemistry*
  • Glutamic Acid / metabolism*
  • Glycerol / chemical synthesis*
  • Glycerol / chemistry
  • Glycerol / pharmacology*
  • Glycerol / therapeutic use
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Mice
  • Nitric Oxide / metabolism*
  • Pain / drug therapy*
  • Pain / metabolism
  • Selenium / chemistry*

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Ethers
  • Nitric Oxide
  • Glutamic Acid
  • Selenium
  • Glycerol