TY - JOUR T1 - Inhibition of NO Production in LPS-stimulated Mouse Macrophage-like Cells by Trihaloacetylazulenes JF - Anticancer Research JO - Anticancer Res SP - 2921 LP - 2927 VL - 26 IS - 4B AU - NOBUHARU OHSHIMA AU - YOSHIAKI AKATSU AU - MASAYUKI NISHISHIRO AU - HIDETSUGU WAKABAYASHI AU - TERUO KURIHARA AU - KAZUE SATOH AU - NOBORU MOTOHASHI AU - KEN HASHIMOTO AU - HIROSHI SAKAGAMI Y1 - 2006/07/01 UR - http://ar.iiarjournals.org/content/26/4B/2921.abstract N2 - 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. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -