Design, synthesis, and structure-activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury

Drug Des Devel Ther. 2018 Apr 19:12:887-899. doi: 10.2147/DDDT.S160314. eCollection 2018.

Abstract

Purpose: The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury.

Methods: A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages.

Results: Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f, was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway.

Conclusion: The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury.

Keywords: acute lung injury; anti-inflammation; drug design; indanone; synthesis.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / pathology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Indans / chemical synthesis
  • Indans / chemistry
  • Indans / pharmacology*
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • 2-benzylidene-1-indanone
  • Anti-Inflammatory Agents, Non-Steroidal
  • Indans