Anti-inflammatory activities of melatonin derivatives in lipopolysaccharide-stimulated RAW 264.7 cells and antinociceptive effects in mice

Drug Dev Res. 2014 Jun;75(4):235-45. doi: 10.1002/ddr.21177. Epub 2014 May 14.

Abstract

Preclinical Research This study describes the anti-inflammatory activities of two semisynthesized melatonin (MT) derivatives, benzoyl-melatonin (BMT) and acetyl-melatonin (AMT), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage cells (RAW 264.7) and their antinociceptive effects in mice. The MT derivatives inhibited production of nitric oxide NO and prostaglandin E2 in LPS-stimulated RAW264.7 cells in a dose-dependent manner with IC50 values lower than those of MT. BMT produced increased tail flick latency time, decreased number of writhes, and reduced nociceptive response in mice when compared with AMT and MT. BMT and AMT had enhanced anti-inflammatory effects in LPS-stimulated RAW264.7 compared with MT. However, in mouse studies BMT exhibited the highest potency as an anti-inflammatory agent and was longer-acting as an antinociceptive compound compared with AMT or MT, suggesting that BMT has potential as an anti-inflammatory and analgesic compound.

Keywords: acetyl; anti-inflammatory; antinociceptive; benzoyl; melatonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Male
  • Melatonin / administration & dosage
  • Melatonin / analogs & derivatives*
  • Melatonin / chemical synthesis*
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred ICR
  • Pain / drug therapy*

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • N-(2-(1-acetyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide
  • N-(2-(1-benzoyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide
  • Melatonin