Semisynthesis, an Anti-Inflammatory Effect of Derivatives of 1β-Hydroxy Alantolactone from Inula britannica

Molecules. 2017 Oct 27;22(11):1835. doi: 10.3390/molecules22111835.

Abstract

1β-hydroxy alantolactone, a sesquiterpene lactone mainly isolated from Inula genus plants, exhibits potent anti-inflammatory and anticancer activities. In this work, 1β-hydroxy alantolactone was isolated and five derivatives were prepared through different reactions at the C1-OH and C13-methylene motifs. The structure-activity relationships (SAR) of anti-inflammatory effects against NO production in RAW264.7 cells showed that the α-methylene-γ-butyrolactone motif was essential for NO production suppression and that retaining the C1-OH group can remarkably improve this effect. The NF-κB signaling pathway plays a pivotal role in the regulation of NO expression. Moreover, the levels of p65 and p50 phosphorylation were investigated and active compound 1 inhibited phosphorylation of p65 and p50 in TNF-α-induced NF-κB signaling. Further molecular docking suggested that 1 may target the p65 of NF-κB.

Keywords: 1β-hydroxy alantolactone; anti-inflammatory activity; semisynthesis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Gene Expression
  • Genes, Reporter
  • Inhibitory Concentration 50
  • Inula / chemistry*
  • Lactones / chemical synthesis
  • Lactones / chemistry*
  • Lactones / pharmacology*
  • Mice
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • RAW 264.7 Cells
  • Sesquiterpenes, Eudesmane / chemical synthesis
  • Sesquiterpenes, Eudesmane / chemistry*
  • Sesquiterpenes, Eudesmane / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Lactones
  • NF-kappa B
  • Sesquiterpenes, Eudesmane
  • Nitric Oxide
  • alantolactone