TY - JOUR
T1 - Jacobsen Catalyst as a Cytochrome P450 Biomimetic Model for the Metabolism of Monensin A
AU - Rocha, Bruno Alves
AU - Moraes de Oliveira, Anderson Rodrigo
AU - Pazin, Murilo
AU - Dorta, Daniel Junqueira
AU - Rodrigues, Andresa Piacezzi Nascimento
AU - Berretta, Andresa Aparecida
AU - Peti, Ana Paula Ferranti
AU - Beraldo de Moraes, Luiz Alberto
AU - Lopes, Norberto Peporine
AU - Gates, Paul Jonathan
AU - Assis, Marilda das Dores
AU - Pospíšil, Stanislav
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - TANDEM MASS-SPECTROMETRY
KW - IN-VITRO METABOLISM
KW - PLASMODIUM-FALCIPARUM
KW - IONOPHORE ANTIBIOTICS
KW - OXIDATIVE STRESS
KW - MITOCHONDRIAL
KW - TOXICITY
KW - CELLS
KW - RHABDOMYOLYSIS
KW - FRAGMENTATION
U2 - 10.1155/2014/152102
DO - 10.1155/2014/152102
M3 - Article (Academic Journal)
C2 - 24987668
SN - 2314-6133
JO - BioMed Research International
JF - BioMed Research International
M1 - 152102
ER -