Analogues of 2-phenyl-ethenesulfonic acid phenyl ester have dual functions of inhibiting expression of inducible nitric oxide synthase and activating peroxisome proliferator-activated receptor gamma

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5676-9. doi: 10.1016/j.bmcl.2008.08.107. Epub 2008 Aug 31.

Abstract

We identified a series of 2-phenyl-ethenesulfonic acid phenyl ester analogues as novel dual-function agents that suppressed nitric oxide production in lipopolysaccharide/interferon gamma-stimulated RAW264.7 cells and activated peroxisome proliferator-activated receptor gamma (PPARgamma) in a cell-based transactivation assay. Western blot analysis demonstrated that these compounds inhibit the expression of inducible nitric oxide synthase protein, and scintillation proximity assay validated their ability to bind to PPARgamma. Our studies provide the basis for developing these dual-function agents for anti-inflammation and anti-atherosclerosis therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanesulfonates / chemical synthesis*
  • Alkanesulfonates / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Enzyme Activation
  • Esters / chemistry*
  • Inhibitory Concentration 50
  • Mice
  • Models, Chemical
  • Nitric Oxide / chemistry
  • Nitric Oxide Synthase Type II / biosynthesis*
  • PPAR gamma / biosynthesis*
  • Sulfonic Acids / chemistry
  • Transcriptional Activation

Substances

  • Alkanesulfonates
  • Anti-Inflammatory Agents
  • Esters
  • PPAR gamma
  • Sulfonic Acids
  • Nitric Oxide
  • Nitric Oxide Synthase Type II