PT  - JOURNAL ARTICLE
AU  - TAKAHASHI, JURI
AU  - SEKINE, TAKASHI
AU  - NISHISHIRO, MASAYUKI
AU  - ARAI, ATSUHIRO
AU  - WAKABAYASHI, HIDETSUGU
AU  - KURIHARA, TERUO
AU  - HASHIMOTO, KEN
AU  - SATOH, KAZUE
AU  - MOTOHASHI, NOBORU
AU  - SAKAGAMI, HIROSHI
TI  - Inhibition of NO Production in LPS-stimulated Mouse Macrophage-like Cells by Trihaloacetylazulene Derivatives
DP  - 2008 Jan 01
TA  - Anticancer Research
PG  - 171--178
VI  - 28
IP  - 1A
4099  - http://ar.iiarjournals.org/content/28/1A/171.short
4100  - http://ar.iiarjournals.org/content/28/1A/171.full
SO  - Anticancer Res2008 Jan 01; 28
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).