RT Journal Article
SR Electronic
T1 Inhibition of NO Production in LPS-stimulated Mouse Macrophage-like Cells by Trihaloacetylazulenes
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2921
OP 2927
VO 26
IS 4B
A1 NOBUHARU OHSHIMA
A1 YOSHIAKI AKATSU
A1 MASAYUKI NISHISHIRO
A1 HIDETSUGU WAKABAYASHI
A1 TERUO KURIHARA
A1 KAZUE SATOH
A1 NOBORU MOTOHASHI
A1 KEN HASHIMOTO
A1 HIROSHI SAKAGAMI
YR 2006
UL http://ar.iiarjournals.org/content/26/4B/2921.abstract
AB 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