Novel anti-inflammatory chalcone derivatives inhibit the induction of nitric oxide synthase and cyclooxygenase-2 in mouse peritoneal macrophages

FEBS Lett. 1999 Jun 18;453(1-2):129-34. doi: 10.1016/s0014-5793(99)00707-3.

Abstract

In a previous work, we tested a series of chalcone derivatives as possible anti-inflammatory compounds. We now investigate the effects of three of those compounds, CHI, CH8 and CH12, on nitric oxide and prostanoid generation in mouse peritoneal macrophages stimulated with lipopolysaccharide and in the mouse air pouch injected with zymosan, where they showed a dose-dependent inhibition with inhibitory concentration 50% values in the microM range. This effect was not the consequence of a direct inhibitory action on enzyme activities. Our results demonstrated that chalcone derivatives inhibited de novo inducible nitric oxide synthase and cyclooxygenase-2 synthesis, being a novel therapeutic approach for inflammatory diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Chalcone / analogs & derivatives*
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Female
  • Isoenzymes / biosynthesis*
  • Lipopolysaccharides / pharmacology
  • Macrophages, Peritoneal / enzymology*
  • Mice
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type II
  • Nitrites / metabolism
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Zymosan / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Isoenzymes
  • Lipopolysaccharides
  • Nitrites
  • Chalcone
  • Zymosan
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone