Benzothiazolium compounds: novel classes of inhibitors that suppress the nitric oxide production in RAW264.7 cells stimulated by LPS/IFNgamma.
A series of benzothiazolium compounds were identified as novel classes of inhibitors of nitric oxide production in a cell culture system. They exhibited approximately 1600 folds potency with IC(50) at approximately 50nM to several microM as compared to IC(50) 88.4microM of l-NMMA, a known inhibitor of nitric oxide synthase. The mechanistic studies suggest that decreased iNOS protein synthesis and mRNA transcription, at least in part, were related to the inhibitory activity of effective benzothiazolium compounds. The correlation of in vivo and in vitro activities using mouse paw edema model was also demonstrated.
Tseng
Huan-Yi
HY
Division of Biotechnology and Pharmaceutical Researches, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan, ROC.
Wu
Ssu-Hui
SH
Huang
Wen-Hsin
WH
Wang
Shao-Fang
SF
Yang
Yung-Ning
YN
Mahindroo
Neeraj
N
Hsu
Tsu
T
Jiaang
Weir-Torn
WT
Lee
Shiow-Ju
SJ
D000818:Animals; D052160:Benzothiazoles; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology
D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D013844:Thiazoles; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C005465:benzothiazole