Aplicação do modelo microbiano do metabolismo animal ao estudo da biotransformação de um potencial agente cardioativo

• Autor(a) principal: Carneiro, Emmanuel de Oliveira
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/0013000005j05
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/12100
• topic: Metabolismo; Biotransformação microbiana; Beauveria bassiana; LASSBio-294; Metabolism; Microbial biotransformation; Beauveria bassiana; LASSBio-294; CIENCIAS DA SAUDE::FARMACIA

Drug metabolism, or biotransformation, is the enzymatically catalyzed conversion of a drug to a chemically distinct product, known generically as metabolite. The biotransformation impact on drugs biological fate makes essential to study it in the early stages of drug development. Traditionally, in vivo metabolism are conducted in animal models, whose biological fluids are examined for metabolites identification. The observation that simple microorganisms can mimic most of the phase I and some phase II reactions performed in mammals has shown they represent an alternative to produce high amounts of metabolites in vitro. The main organisms used are filamentous fungi, with particular attention to Beauveria bassiana and the genus Cunninghamella. The aim of this work is the application of B. bassiana as a microbial model to study LASSBio-294 biotransformation profile in parallel to an animal model. This substance has demonstrated significant positive inotropic and vasodilatory properties, turning it a potential cardioactive prototype. A capsule with LASSBio-294 was administered to a dog in a pilot study and analyzed by High Performance Liquid Chromatography with Ultraviolet detection (HPLCUV). B. bassiana ATCC 7159 incubation supernatant samples were taken and analyzed by HPLC- UV. At the end of the process, formed metabolites were extracted and purified. One product was characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). According to the HPLC-UV analysis, B. bassiana ATCC 7159 produced a major metabolite detected in higher concentration after 24 hours of incubation. This metabolite was the same detected in dog serum samples. The biosynthesis of this metabolite resulted in a yield of 6%. The spectral data show the produced metabolite by dog and B. bassiana ATCC 7159 is a LASSBio-294 sulfoxide derivative. In vitro biosynthesis allowed to obtain, in considerable yield, the main mammalian metabolite detected in the in vivo method.