Anti-inflammatory activity of the synthetic chalcone derivatives: inhibition of inducible nitric oxide synthase-catalyzed nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells

Biol Pharm Bull. 2007 Aug;30(8):1450-5. doi: 10.1248/bpb.30.1450.


Chalcones belong to the flavonoid family from plant origin and some of them possess anti-inflammatory activity. Recently, several natural and synthetic chalcone derivatives were reported to inhibit inducible nitric oxide synthase (iNOS)-catalyzed NO production in cell cultures. In the present study, to find the optimal chemical structures and to elucidate their action mechanisms, 41 synthetic chalcones having the substituent(s) on A- and B-rings were prepared and their effects on iNOS-catalyzed NO production were evaluated using lipopolysaccharide (LPS)-treated RAW 264.7 cells. When simultaneously added with LPS, 2'-methoxy-3,4-dichlorochalcone (Ch15), 2'-hydroxy-6'-methoxychalcone (Ch29), 2'-hydroxy-3-bromo-6'-methoxychalcone (Ch31) and 2'-hydroxy-4',6'-dimethoxychalcone (Ch35) among the tested compounds potently inhibited NO production (IC(50)s, 7.1-9.6 muM). The favorable chemical structures were found to be a methoxyl substitution in A-ring at an adjacent position (2' or 6') to carbonyl moiety with/without 2'-(or 6'-)hydroxyl group and 3-halogen substitution in B-ring. When the cellular action mechanisms of Ch15, Ch31 and Ch35 were further examined using Western blotting and electrophoretic mobility shift assay, it was revealed that Ch15 and Ch31 clearly down-regulated iNOS expression while Ch35 did not. Moreover, Ch15 and Ch31 were proved to suppress the nuclear transcription factor-kappaB activation. From the results, it is suggested that certain chalcone derivatives potently inhibit iNOS-catalyzed NO production by the different cellular mechanisms, iNOS down-regulation and/or iNOS inhibition, depending on their chemical structures. These chalcone derivatives may possibly be used as lead compounds for developing new anti-inflammatory agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blotting, Western
  • Cell Line
  • Chalcones / pharmacology*
  • Down-Regulation / drug effects
  • Electrophoretic Mobility Shift Assay
  • Lipopolysaccharides / pharmacology*
  • Macrophages / enzymology
  • Macrophages / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Structure-Activity Relationship


  • Anti-Inflammatory Agents, Non-Steroidal
  • Chalcones
  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide
  • Nitric Oxide Synthase Type II