A method for screening hypochlorous acid scavengers by inhibition of the oxidation of 5-thio-2-nitrobenzoic acid: application to anti-asthmatic drugs.
Neutrophils use a bactericidal mechanism through the release of the enzyme myeloperoxidase which catalyzes the formation of the powerful oxidant hypochlorous acid (HOCl) from H2O2 and Cl-. HOCl can inactivate alpha 1-antiproteinase (alpha 1-AP) which causes increased proteolytic activity at sites of pulmonary inflammation. The search for possible HOCl scavengers usually involves time-consuming enzyme assays (e.g., alpha 1-AP and elastase). We developed a method in which the compound 5-thio-2-nitrobenzoic acid could easily be oxidized by HOCl. The inhibition of this oxidation by a test compound is a measurement of its HOCl scavenging activity. To illustrate the method we tested some well-known HOCl scavengers such as S-methylated glutathione and oxidized lipoate. Finally several anti-asthmatic drugs such as terbutaline, isoproterenol, salbutamol, cromoglycate, theophylline, and dexamethasone were evaluated. Only the drug terbutaline acted as a HOCl scavenger.
Ching
T L
TL
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, The Netherlands.
de Jong
J
J
Bast
A
A
D001993:Bronchodilator Agents / Q000494:pharmacology*; D016166:Free Radical Scavengers; D006997:Hypochlorous Acid / Q000737:chemistry* / Q000378:metabolism; D009579:Nitrobenzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013438:Sulfhydryl Compounds
D001993:Bronchodilator Agents; D016166:Free Radical Scavengers; D009579:Nitrobenzoates; D013438:Sulfhydryl Compounds; C011136:thionitrobenzoic acid; D006997:Hypochlorous Acid