RT Journal Article
SR Electronic
T1 Inhibition of LPS-stimulated NO Production in Mouse Macrophage-like Cells by Azulenequinones
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4157
OP 4163
VO 25
IS 6B
A1 NISHISHIRO, MASAYUKI
A1 ARIKAWA, SATOMI
A1 WAKABAYASHI, HIDETSUGU
A1 HASHIMOTO, KEN
A1 SATOH, KAZUE
A1 YOKOYAMA, KEIKO
A1 UNTEN, SENWA
A1 KAKUTA, HANZO
A1 KURIHARA, TERUO
A1 MOTOHASHI, NOBORU
A1 SAKAGAMI, HIROSHI
YR 2005
UL http://ar.iiarjournals.org/content/25/6B/4157.abstract
AB Azulenequinone derivatives have been reported to display a broad spectrum of biological activities, but study at the cellular level has been limited. The effect of twenty-seven azulenequinone derivatives on nitric oxide (NO) production by mouse macrophage-like cells Raw 264.7 was investigated in this study. All of these compounds failed to stimulate the Raw 264.7 cells to produce detectable amounts of NO, but did inhibit NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to varying extents. Compounds [7, 8, 9, 13, 16, 25, 27], which showed lesser cytotoxic activity (CC50=425, 381, 482, 179, 119, 235, 225 μM, respectively), inhibited NO production to the greatest extent [selectivity index (SI)= 15.4, 26.2, 3.9, 21.6, 3.1, 6.0, 8.4, respectively]. Western blot and RT-PCR analyses demonstrated that the most active derivatives, 3-morpholino-1,5-azulenequinone [8] and 3,7-dibromo-1,5-azulenequinone [13], significantly reduced both the intracellular concentration of iNOS protein and the expression of iNOS mRNA. ESR spectroscopy showed that compounds [8, 13] weakly scavenged NO produced by NOC-7, possibly via their general reducing activity. These data suggest that the inhibitory effect of NO production by compounds [8, 13] might be generated mostly via the inhibition of iNOS expression, rather than the radical-mediated mechanism. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved