7-NITRO INDAZOLE DERIVATIVES ARE POTENT INHIBITORS OF BRAIN, ENDOTHELIUM AND INDUCIBLE ISOFORMS OF NITRIC-OXIDE SYNTHASE

被引：79

作者：

BLANDWARD, PA ^{[1
]}

MOORE, PK ^{[1
]}

机构：

[1] UNIV LONDON KINGS COLL, DIV BIOMED SCI, PHARMACOL GRP, LONDON SW3 6LX, ENGLAND

来源：

LIFE SCIENCES | 1995年 / 57卷 / 11期

关键词：

INDAZOLE; NITRIC OXIDE SYNTHASE; CEREBELLUM; ENDOTHELIAL CELLS;

D O I：

10.1016/0024-3205(95)02046-L

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The effect of 7-nitro indazole (7-NI) and a range of substituted indazole derivatives on nitric or;ide synthase (NOS) enzyme activity in homogenates of rat cerebellum, bovine endothelial cells and lung from endotoxin-pretreated rats was investigated. 3-bromo 7-nitro indazole was either equipotent (IC50, 0.86 +/- 0.05 mu M c.f. 0.78 +/- 0.2 mu M, n=6, P>0.05) or approximately 4x (IC50, 0.17 = 0.01 mu M c.f. 0.71 +/- 0.01 mu M, n=6, P<0.05) or 20x(IC50, 0.29 +/- 0.01 mu M c.f. 5.8 +/- 0.4 mu M, n=6, P<0.05) more potent than 7-NI as an inhibitor of bovine endothelial, rat cerebellar and rat lung NOS enzyme activity respectively. 2,7-dinitro indazole also inhibited NOS in all three tissue sources with a potency similar to that of 7-NI. These results suggest that 3-bromo 7-NI and 2,7-dinitro indazole may prove to be useful additional tools with which to examine the biological properties of nitric oxide (NO).

引用

页码：PL131 / PL135

页数：5

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