Synthesis of biflavones having a 6-O-7'' linkage and effects on cyclooxygenase-2 and inducible nitric oxide synthase

Bioorg Med Chem Lett. 2009 Jan 1;19(1):74-6. doi: 10.1016/j.bmcl.2008.11.017. Epub 2008 Nov 12.

Abstract

In order to establish anti-inflammatory potential of biflavonoids, 17 biflavone derivatives having a 6-O-7'' linkage were synthesized and their effects on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were evaluated. The basic molecule (6-O-7'' biflavone) potently inhibited COX-2-mediated PGE(2) production (IC(50): <2 microM), being less active on iNOS-mediated NO production (IC(50): >50 microM) from lipopolysaccharide-treated RAW 264.7 cells, a mouse macrophage cell line. Generally, the hydroxyl/methoxyl substitution(s) on the basic biflavone (6-O-7'') reduced the inhibitory activity of PGE(2) production, while the effects on NO production were varied. It is suggested that the basic biflavone (6-O-7'') may have a potential for new anti-inflammatory agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Biflavonoids / chemical synthesis*
  • Cell Line
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / biosynthesis
  • Flavones / chemical synthesis
  • Inhibitory Concentration 50
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents
  • Biflavonoids
  • Cyclooxygenase 2 Inhibitors
  • Flavones
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Dinoprostone