7-Nitro indazole derivatives are potent inhibitors of brain, endothelium and inducible isoforms of nitric oxide synthase.
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).
Bland-Ward
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Biomedical Sciences Division, King's College, University of London, U.K.
Moore
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000818:Animals; D002417:Cattle; D002531:Cerebellum / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar
D007191:Indazoles; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C080122:7-nitroindazole