RT Journal Article
SR Electronic
T1 Inhibition of NO Production in LPS-stimulated Mouse Macrophage-like Cells by Trihaloacetylazulene Derivatives
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 171
OP 178
VO 28
IS 1A
A1 TAKAHASHI, JURI
A1 SEKINE, TAKASHI
A1 NISHISHIRO, MASAYUKI
A1 ARAI, ATSUHIRO
A1 WAKABAYASHI, HIDETSUGU
A1 KURIHARA, TERUO
A1 HASHIMOTO, KEN
A1 SATOH, KAZUE
A1 MOTOHASHI, NOBORU
A1 SAKAGAMI, HIROSHI
YR 2008
UL http://ar.iiarjournals.org/content/28/1A/171.abstract
AB The effect of 20 trihaloacetylazulene derivatives with one halogen atom, on nitric oxide (NO) production by mouse macrophage-like cells Raw 264.7 was investigated. 2-Methoxyazulenes and 2-ethoxyazulenes exhibited comparable cytotoxicity. Trichloroacetylazulenes generally exhibited higher cytotoxicity, as compared with the corresponding trifluoroacetylazulenes. Substitution of chloride, bromide or iodine at the C-3 position further enhanced their cytotoxicity. All of these compounds failed to stimulate the Raw 264.7 cells to produce detectable amounts of NO, but did inhibit NO production by LPS-activated Raw 264.7 cells to different extents. 1-Trichloroacetyl-2-methoxyazulene and 1-trichloroacetyl-2-ethoxyazulene, with less cytotoxic activity, inhibited NO production to the greatest extent, producing the highest selectivity index (SI) of >24.7 and >28.7, respectively. This was accompanied by the efficient inhibition of inducible NO synthase (iNOS) mRNA expression, but not by iNOS protein abundance. Electron spin resonance (ESR) spectroscopy showed that neither of these compounds produced radicals, nor scavenged NO, superoxide anion or diphenyl-2-picrylhydrazyl radicals. The present study suggests that the inhibitory effects of trifluoroacetylazulenes and trichloroacetylazulenes on NO production by activated macrophages might be derived from the perturbation of NO anabolism (inhibition of iNOS mRNA expression and possibly the inactivation of iNOS protein) rather than NO catabolism (NO scavenging).