7-硝基吲唑衍生物是脑、内皮和诱导型一氧化氮合酶亚型的有效抑制剂。

7-Nitro indazole derivatives are potent inhibitors of brain, endothelium and inducible isoforms of nitric oxide synthase.

作者信息

Bland-Ward P A, Moore P K

机构信息

Biomedical Sciences Division, King's College, University of London, U.K.

出版信息

Life Sci. 1995;57(11):PL131-5. doi: 10.1016/0024-3205(95)02046-l.

DOI:10.1016/0024-3205(95)02046-l

PMID:7544863

Abstract

The effect of 7-nitro indazole (7-NI) and a range of substituted indazole derivatives on nitric oxide 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 microM c.f. 0.78 +/- 0.2 microM, n = 6, P > 0.05) or approximately 4x (IC50, 0.17 +/- 0.01 microM c.f. 0.71 +/- 0.01 microM, n = 6, P < 0.05) or 20x (IC50, 0.29 +/- 0.01 microM c.f. 5.8 +/- 0.4 microM, 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).

摘要

研究了7-硝基吲唑（7-NI）及一系列取代吲唑衍生物对内毒素预处理大鼠的大鼠小脑、牛内皮细胞和肺匀浆中一氧化氮合酶（NOS）酶活性的影响。3-溴-7-硝基吲唑作为牛内皮、大鼠小脑和大鼠肺NOS酶活性的抑制剂，其效力分别与7-NI相当（IC50，0.86±0.05 microM对比0.78±0.2 microM，n = 6，P>0.05），或约为7-NI的4倍（IC50，0.17±0.01 microM对比0.71±0.01 microM，n = 6，P<0.05），或20倍（IC50，0.29±0.01 microM对比5.8±0.4 microM，n = 6，P<0.05）。2,7-二硝基吲唑也抑制了所有三种组织来源的NOS，其效力与7-NI相似。这些结果表明，3-溴-7-NI和2,7-二硝基吲唑可能被证明是用于研究一氧化氮（NO）生物学特性的有用的额外工具。