Inhibition of NO production in LPS-stimulated mouse macrophage-like cells by benzo[b]cyclohept[e] [1,4]oxazine and 2-aminotropone derivatives.
The aim of this study was to investigate whether a total of twenty benzo[b]cyclohept[e][1,4]oxazines and their S-analogs, and 2-aminotropone derivatives affect the function of activated macrophages. These compounds inhibited the production of pro-inflammatory substances such as nitric oxide (NO) by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells to different extents. Among them, benzo[b]cyclohept[e][1,4]oxazin-6(11H)-one [5] and 7-bromo-2-(4-hydroxyanilino)tropone [16] showed the highest inhibitory effects at concentrations that did not affect cellular viability (selectivity index=74.89 and 54.15, respectively). Western blot and RT-PCR analyses showed that [16] inhibited the expression of both inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at both protein and mRNA levels, whereas [5] inhibited only iNOS protein expression. Electron-spin resonance (ESR) spectroscopy revealed that both [5] and [16] scavenged nitric oxide (generated from NOC-7) and superoxide anion (generated by HX-XOD reaction) only at much higher concentration. These data suggest that [16] but not [5] exerts its anti-inflammatory action against macrophages via the inhibition of iNOS and COX-2 protein expressions.
Faculty of Science, Josai University, Sakado, Saitama, Japan.
Akina
A
Suga
Taichi
T
Narita
Li
L
Zhou
Hiroshi
H
Sakagami
Kazue
K
Satoh
Hidetsugu
H
Wakabayashi
D000818:Animals; D001567:Benzocycloheptenes / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology
C532753:2-aminotropone; D001567:Benzocycloheptenes; D008070:Lipopolysaccharides; D010078:Oxazines; D012333:RNA, Messenger; D009569:Nitric Oxide; D014334:Tropolone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2