Effect of tropolone, azulene and azulenequinone derivatives on prostaglandin E2 production by activated macrophage-like cells

Anticancer Res. 2009 Jan;29(1):379-83.


We have previously reported that tropolone (T-3), 2,4-dibromo-7-methoxytropone (T-21), diethyl 2-chloroazulene-1,3-dicarboxylate (A-9), 1,3-difluoroazulene (A-11), 3-morpholino-1,5-azulenequinone (AQ-8) and 3,7-dibromo-1,5-azulenequinone (AQ-13) inhibited the nitric oxide (NO) production of lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells, with or without the inhibition of inducible NO synthase (iNOS) mRNA and protein expression. In order to confirm the anti-inflammatory potency, possible effects on prostaglandin (PG) E2 production and the expression of enzymes involved in the arachidonic acid pathway were investigated. Among these six compounds, only A-9 effectively inhibited the PGE2 production of the LPS-stimulated RAW264.7 cells. Western blot analysis demonstrated that A-9 inhibited phospholipase A2 (PLA2), cyclooxygenase (COX)-2 and iNOS proteins only by 12, 45 and 42%, respectively. These data demonstrate the lack of correlation between the extent of inhibition of iNOS protein expression by tropolone or azulene derivatives and that of PGE2, and suggest the possible antiinflammatory potency of A-9.

MeSH terms

  • Animals
  • Azulenes / pharmacology*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Dinoprostone / biosynthesis*
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / enzymology
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Phospholipase A2 Inhibitors
  • Quinones / pharmacology*
  • Tropolone / analogs & derivatives*
  • Tropolone / pharmacology


  • Azulenes
  • Cyclooxygenase 2 Inhibitors
  • Lipopolysaccharides
  • Phospholipase A2 Inhibitors
  • Quinones
  • Tropolone
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Dinoprostone