Biomimetic modeling of oxidative drug metabolism |
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Authors: | Wiebke Lohmann Uwe Karst |
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Institution: | Westf?lische Wilhelms-Universit?t Münster, Institute of Inorganic and Analytical Chemistry, Corrensstr. 30, 48149, Münster, Germany. |
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Abstract: | The prediction of drug metabolism is an important task in drug development. Besides well-established in vitro and in vivo
methods using biological matrices, several biomimetic models have been developed. This review summarizes three different nonenzymatic
strategies, including metalloporphyrins as surrogates of the active centre of cytochrome P450, Fenton’s reagent, and the electrochemical
oxidation of drug compounds. Although none of the systems can simulate the whole range of cytochrome P450-catalyzed reactions
adequately, the biomimetic models show some advantages over standard in vitro methods. For example, metalloporpyhrin catalysts
allow the synthesis of certain metabolites in sufficient amounts and with sufficient purities to permit characterization and
further pharmacological and toxicological tests. The electrochemical generation of metabolites coupled on-line to liquid chromatography/mass
spectrometry is a promising tool for studying reactive metabolites and can be applied in automated high-throughput screening
approaches. In this paper, detailed comparisons with cytochrome P450 catalysis are drawn, advantages and disadvantages of
the respective methods are revealed, and possible applications are discussed. |
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Keywords: | Drug metabolism Biomimetic oxidations Metalloporphyrins Fenton’ s reagent Electrochemistry/LC/MS |
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