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

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Rocha, Bruno Alves ; Moraes de Oliveira, Anderson Rodrigo ; Pazin, Murilo ; Dorta, Daniel Junqueira ; Rodrigues, Andresa Piacezzi Nascimento ; Berretta, Andresa Aparecida ; Peti, Ana Paula Ferranti ; Beraldo de Moraes, Luiz Alberto ; Lopes, Norberto Peporine ; Pospisil, Stanislav ; Gates, Paul Jonathan ; Assis, Marilda das Dores

• Document type: Journal article
• Source: BIOMED RESEARCH INTERNATIONAL; v. 2014, p. 8-pg., 2014-01-01.

Abstract

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. (AU)

• FAPESP's process: 11/05800-0 - Evaluation of Microbiological and Chemical Models for the Study of Bio(transformations) of Antibiotic Monensin A
• Grantee: Bruno Alves Rocha
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/17658-9 - Development and validation of chromatographic and electrophoretic methods for subsequent application in studies of in vitro metabolism and biotransformation - phase 2
• Grantee: Anderson Rodrigo Moraes de Oliveira
• Support Opportunities: Regular Research Grants