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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Rocha, Bruno Alves [1] ; Moraes de Oliveira, Anderson Rodrigo [1] ; Pazin, Murilo [2] ; Dorta, Daniel Junqueira [1] ; Rodrigues, Andresa Piacezzi Nascimento [3] ; Berretta, Andresa Aparecida [3] ; Peti, Ana Paula Ferranti [1] ; Beraldo de Moraes, Luiz Alberto [1] ; Lopes, Norberto Peporine [4] ; Pospisil, Stanislav [5] ; Gates, Paul Jonathan [6] ; Assis, Marilda das Dores [1]
Total Authors: 12
[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14040901 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Apis Flora Ind & Comercial LTDA, Lab Pesquisa Desenvolvimento & Inovacao, BR-14012067 Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
[5] Acad Sci Czech Republic, Inst Microbiol, CZ-14220 Prague - Czech Republic
[6] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon - England
Total Affiliations: 6
Document type: Journal article
Web of Science Citations: 2

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 type: 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 type: Regular Research Grants