Aplicação do modelo microbiano do metabolismo animal ao estudo da biotransformação de um potencial agente cardioativo
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2011-02-28
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Universidade Federal de Goiás
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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.
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CARNEIRO, E. O. Aplicação do modelo microbiano do metabolismo animal ao estudo da biotransformação de um potencial agente cardioativo. 2011. 104 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2011.