Inhibition of NO Production in LPS-stimulated Mouse Macrophage-like Cells by Trihaloacetylazulenes

The effects of 26 trihaloacetylazulene derivatives on nitric oxide (NO) production by the mouse macrophage-like Raw 264.7 cells was investigated. The trichloroacetylazulenes [1b-13b] generally showed higher cytotoxicity as compared with the corresponding trifluoroacetylazulenes [1a-13a] . All the co...

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Bibliographic Details
Published in:Anticancer research 2006-07, Vol.26 (4B), p.2921-2927
Main Authors: OHSHIMA, Nobuharu, AKATSU, Yoshiaki, NISHISHIRO, Masayuki, WAKABAYASHI, Hidetsugu, KURIHARA, Teruo, SATOH, Kazue, MOTOHASHI, Noboru, HASHIMOTO, Ken, SAKAGAMI, Hiroshi
Format: Article
Language:English
Subjects:
Animals
Azulenes - chemistry
Azulenes - pharmacology
Biological and medical sciences
Blotting, Western
Cell Line
Cyclooxygenase 2 - biosynthesis
Dinoprostone - biosynthesis
Electron Spin Resonance Spectroscopy
Free Radical Scavengers - pharmacology
Lipopolysaccharides - pharmacology
Macrophages - drug effects
Macrophages - enzymology
Macrophages - metabolism
Medical sciences
Mice
Nitric Oxide - antagonists & inhibitors
Nitric Oxide - biosynthesis
Nitric Oxide Synthase Type II - biosynthesis
Structure-Activity Relationship
Tumors
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Summary:The effects of 26 trihaloacetylazulene derivatives on nitric oxide (NO) production by the mouse macrophage-like Raw 264.7 cells was investigated. The trichloroacetylazulenes [1b-13b] generally showed higher cytotoxicity as compared with the corresponding trifluoroacetylazulenes [1a-13a] . All the compounds inhibited NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to various extents. 3-Trifluoroacetylguaiazulene [8a] , 1-trifluoroacetyl-4,6,8-trimethylazulene [10a] , 3-methyl-1-trichloroacetylazulene [2b] and 3-ethyl-1-trichloroacetylazulene [3b] showed lower cytotoxic activity and most effectively inhibited NO production. Western blot analysis revealed that compounds [8a, 10a] dose-dependently reduced the intracellular concentration of inducible NO synthase (iNOS), whereas compounds [2b, 3b] only marginally affected the iNOS protein expression. RT-PCR analysis showed that compounds [8a, 2b] reduced the iNOS mRNA expression by approximately 50%. These compounds affected cyclooxygenase-2 protein and mRNA expression, depending on the concentrations. ESR spectroscopy revealed that compounds [8a, 10a, 2b, 3b] neither produced radical, nor scavenged NO, superoxide anion or diphenyl-2-picrylhydrazyl radicals. The present study showed the inhibitory effects of trifluoroacetylazulenes and trichloroacetylazulenes on NO production by activated macrophages.
ISSN:0250-7005
1791-7530