Synthesis and biological evaluation of diarylheptanoids as potential antioxidant and anti-inflammatory agents

Eur J Med Chem. 2018 Jan 20:144:289-299. doi: 10.1016/j.ejmech.2017.12.033. Epub 2017 Dec 11.

Abstract

Reactive oxygen species (ROS) are key signaling molecules and their overproduction plays an important role in the inflammation process, the secretion of inflammatory cytokines such as IL-1β and IL-6 and the progression of inflammatory disorders. Decreasing oxidative stress represents a promising challenge in the design of antioxidant and anti-inflammatory agents. In the present study, a series of new diarylheptanoids containing allylic alcohol, amide, hydantoin or triazole fragments were synthesized and fully characterized. We evaluated the ability of these agents to block the production of intracellular ROS and the subsequent inflammatory events exerted by lipopolysaccharide (LPS) on murine macrophage RAW 264.7. Five diarylheptanoids were found to exhibit the dual required properties.

Keywords: Anti-inflammatory activity; Antioxidant; Diarylheptanoid; Macrocycle.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Diarylheptanoids / chemical synthesis
  • Diarylheptanoids / chemistry
  • Diarylheptanoids / pharmacology*
  • Dose-Response Relationship, Drug
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Mice
  • Molecular Structure
  • RAW 264.7 Cells
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Diarylheptanoids
  • Lipopolysaccharides
  • Reactive Oxygen Species