Horseradish Peroxidase-Catalyzed Oxidation of Rifampicin : Reaction Rate Enhancement by Co-oxidation with Anti-inflammatory Drugs(Biochemistry)
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概要
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The tuberculostatic drug rifampicin has been described as a scavenger of reactive species. Additionally, the recent demonstration that oral therapy with a complex of rifampicin and horseradish peroxidase (HRP) was more effective than rifampicin alone, in an animal model of experimental leprosy, suggested the importance of redox reactions involving rifampicin and their relevance to the mechanism of action. Hence, we studied the oxidation of rifampicin catalyzed by HRP, since this enzyme may represent the prototype of peroxidation-mediated reactions. We found that the antibiotic is efficiently oxidized and that rifampicin-quinone is the product, in a reaction dependent on both HRP and hydrogen peroxide. The steady-state kinetic constants K^<app>_m (101±23μmol/l), V^<app>_<max> (0.78±0.09μmol/l・s^<-1>) and k_<cat> (5.1±0.6s^<-1>) were measured (n=4). The reaction rate was increased by the addition of co-substrates such as tetramethylbenzidine, salicylic acid, 5-aminosalicylic acid and paracetamol. This effect was explained by invoking an electron-transfer mechanism by which these drugs acted as mediators of rifampicin oxidation. We suggested that this drug interaction might be important at the inflammatory site.
- 公益社団法人日本薬学会の論文
- 2005-10-01
著者
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Faria Oliveira
Department Of Biochemistry And Chemistry Technology Institute Of Chemistry Unesp-sao Paulo State Uni
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SANTOS Fernanda
Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, UNESP-Sao Paulo State Universit
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XIMENES Valdecir
Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, UNESP-Sao Paulo State Universit
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FONSECA Luiz
Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, UNESP-Sao Paulo State Universit
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BRUNETTI Iguatemy
Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, UNESP-Sao Paulo State Universit
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Brunetti Iguatemy
Department Of Clinical Analysis Faculty Of Pharmaceutical Sciences Unesp-sao Paulo State University
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Fonseca Luiz
Department Of Clinical Analysis Faculty Of Pharmaceutical Sciences Unesp-sao Paulo State University
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Fonseca Luiz
Department Of Clinical Analysis (lac) State University Of Sao Paulo (unesp) School Of Pharmaceutical
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Santos Fernanda
Department Of Clinical Analysis Faculty Of Pharmaceutical Sciences Unesp-sao Paulo State University
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Santos Fernanda
Departamento De Zoologia Da Universidade Federal Do Rio Grande Do Sul
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Ximenes Valdecir
Department Of Clinical Analysis Faculty Of Pharmaceutical Sciences Unesp-sao Paulo State University
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Da Fonseca
Department Of Pediatric Surgery Federal University Of Sao Paulo Escola Paulista De Medicina
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Dos Santos
Departamento De Analises Clinicas Toxicologicas E Bromatologicas Faculdade De Ciencias Farmaceuticas
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XIMENES Valdecir
Department of Clinical Analysis (LAC), State University of Sao Paulo (UNESP), School of Pharmaceutical Science
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