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

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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number152102
Number of pages8
JournalBioMed Research International
DOIs
Publication statusPublished - 2014

Keywords

  • TANDEM MASS-SPECTROMETRY
  • IN-VITRO METABOLISM
  • PLASMODIUM-FALCIPARUM
  • IONOPHORE ANTIBIOTICS
  • OXIDATIVE STRESS
  • MITOCHONDRIAL
  • TOXICITY
  • CELLS
  • RHABDOMYOLYSIS
  • FRAGMENTATION

Cite this