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

• Published in: BioMed research international 2014-01, Vol.2014 (2014), p.1-8
• Main Authors: de Moraes, Luiz Alberto Beraldo, Lopes, Norberto Peporine, Pospíšil, Stanislav, Gates, Paul Jonathan, Assis, Marilda das Dores, Rocha, Bruno Alves, Peti, Ana Paula Ferranti, Berretta, Andresa Aparecida, Rodrigues, Andresa Piacezzi Nascimento, de Oliveira, Anderson Rodrigo Moraes, Pazin, Murilo, Dorta, Daniel Junqueira
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics; Antifungal Agents - pharmacokinetics; Antifungal Agents - pharmacology; Antimicrobial agents; Bacteria - growth & development; Biological activity; Cytochrome P-450; Cytochrome P-450 Enzyme System - metabolism; Drug metabolism; Enzymes; Escherichia coli; Gram-positive bacteria; Metabolism; Metabolites; Microorganisms; Mitochondria, Liver - metabolism; Models, Biological; Monensin; Monensin - pharmacokinetics; Monensin - pharmacology; Oxidation-Reduction - drug effects; Pharmaceutical research; Physiological aspects; Pseudomonas aeruginosa; Rats; Staphylococcus aureus; Staphylococcus epidermidis; Streptomyces; Studies
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/152102

Monensin A is a commercially important natural product isolated from Streptomyces cinnamonensins 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-O-demethyl monensin A and 12-hydroxy monensin A, which are the same ones found in in vivo models. Monensin A and products obtained in biomimetic model were tested in a mitochondrial toxicity model assessment and an antimicrobial bioassay against Staphylococcus aureus, S. aureus methicillin-resistant, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli. 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.