Jacobsen Catalyst as a Cytochrome P450 Biomimetic Model for the Metabolism of Monensin A

BioMed Research International
2014.0

Abstract

<jats:p>Monensin A is a commercially important natural product isolated from<jats:italic>Streptomyces cinnamonensins</jats:italic>that is primarily employed to treat coccidiosis. Monensin A selectively complexes and transports sodium cations across lipid membranes and displays a variety of biological properties. In this study, we evaluated the Jacobsen catalyst as a cytochrome P450 biomimetic model to investigate the oxidation of monensin A. Mass spectrometry analysis of the products from these model systems revealed the formation of two products: 3-<jats:italic>O</jats:italic>-demethyl monensin A and 12-hydroxy monensin A, which are the same ones found in<jats:italic>in vivo</jats:italic>models. Monensin A and products obtained in biomimetic model were tested in a mitochondrial toxicity model assessment and an antimicrobial bioassay against<jats:italic>Staphylococcus aureus, S. aureus</jats:italic>methicillin-resistant,<jats:italic>Staphylococcus epidermidis, Pseudomonas aeruginosa,</jats:italic>and<jats:italic>Escherichia coli.</jats:italic>Our results demonstrated the toxicological effects of monensin A in isolated rat liver mitochondria but not its products, showing that the metabolism of monensin A is a detoxification metabolism. In addition, the antimicrobial bioassay showed that monensin A and its products possessed activity against Gram-positive microorganisms but not for Gram-negative microorganisms. The results revealed the potential of application of this biomimetic chemical model in the synthesis of drug metabolites, providing metabolites for biological tests and other purposes.

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