Synthesis and structure-activity relationships of guaiane-type sesquiterpene lactone derivatives with respect to inhibiting NO production in lipopolysaccharide-induced RAW 264.7 macrophages

Eur J Med Chem. 2014 Aug 18:83:307-16. doi: 10.1016/j.ejmech.2014.06.043. Epub 2014 Jun 21.

Abstract

A guaiane framework was scaffolded by photochemical rearrangement reactions using α-santonin 1 as a starting material. Then, using a series of reactions, we synthesized the guaiane-type sesquiterpene lactone 5 in high yield. The inhibitory activities of compound 5 and of a series of derivatives on nitric oxide (NO) release were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Compounds 6g, 7h, 7i, 7k and 8g, exhibited significant inhibitory effects on NO production, with IC50 values of 14.8, 22.3, 18.3, 17.4 and 7.0 μM, respectively. Their cytotoxicities were also estimated using an MTT assay. The structure-activity relationships of these compounds were also discussed.

Keywords: Guaiane-type derivatives; Inhibitory effect; Nitric oxide production; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemistry Techniques, Synthetic
  • Lactones / chemistry*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / metabolism*
  • Mice
  • Nitric Oxide / biosynthesis*
  • Sesquiterpenes, Guaiane / chemical synthesis
  • Sesquiterpenes, Guaiane / chemistry*
  • Sesquiterpenes, Guaiane / pharmacology*
  • Sesquiterpenes, Guaiane / toxicity
  • Structure-Activity Relationship

Substances

  • Lactones
  • Lipopolysaccharides
  • Sesquiterpenes, Guaiane
  • guaiane
  • Nitric Oxide