Biomimetic oxidation studies of monensin A catalyzed by metalloporphyrins: Identification of hydroxyl derivative product by electrospray tandem mass spectrometry

Sousa-Junior, José N.; Rocha, Bruno Alves; Assis, Marilda das Dores; Peti, Ana Paula Ferranti; Moraes, Luiz Alberto Beraldo de; Iamamoto, Yassuko; Gates, Paul J.; Oliveira, Anderson Rodrigo Moraes de; Lopes, Norberto P.

doi:10.1590/s0102-695x2013005000053

Cited by 6 publications

(6 citation statements)

References 41 publications

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“…The analysis resulted in the [M + Na] + signal at m / z 679.4008 for product 1 (3- O -demethyl monensin A) and m / z 709,4134 for product 2 (12-hydroxy monensin A) confirming the molecular formula (mass error < 5 ppm) the same as observed for the products obtained from in vitro metabolism of monensin A by human liver microsomes and microbial transformation by fungi of Cunninghamella genus [21]. Additionally, products 1 and 2 displayed an identical low-resolution product ion spectrum (Supplementary Materials) as well as having the same retention times as those observed in the previous studies [21, 22]. The major ion formed in the MS/MS studies results from a Grob-Wharton type fragmentation and/or H 2 O, followed by CO elimination, as previously proposed for monensin A and its metabolites (Table 1) [21, 22, 28, 29].…”

Section: Resultssupporting

confidence: 82%

“…Additionally, products 1 and 2 displayed an identical low-resolution product ion spectrum (Supplementary Materials) as well as having the same retention times as those observed in the previous studies [21, 22]. The major ion formed in the MS/MS studies results from a Grob-Wharton type fragmentation and/or H 2 O, followed by CO elimination, as previously proposed for monensin A and its metabolites (Table 1) [21, 22, 28, 29]. …”

Section: Resultssupporting

confidence: 68%

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

Rocha

Oliveira

Pazin

et al. 2014

BioMed Research International

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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.

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Section: Resultssupporting

confidence: 82%

Section: Resultssupporting

confidence: 68%

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

Rocha

Oliveira

Pazin

et al. 2014

BioMed Research International

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“…For monensin, in contrast, the ether rings are easily activated . Because of these properties, the fragmentations of monensin and its derivatives have been thoroughly studied and some metabolites were successfully elucidated . This could not be done in this study, as well as in some previously reported research on salinomycin metabolites, as directly mentioned in an opinion by the European Food Safety Authority…”

Section: Resultsmentioning

confidence: 88%

Identification of metabolites of anticancer candidate salinomycin using liquid chromatography coupled with quadrupole time‐of‐flight and hybrid triple quadrupole linear ion trap mass spectrometry

Olejnik

Radko

Jedziniak

2018

Rapid Comm Mass Spectrometry

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“…Three metabolites of MON A were well known by literature and described as main metabolites [28], an O -demethylated one ( m/z = 679), a hydroxylated one ( m/z = 709) and an O-demethylated-hydroxylated one ( m/z = 695). These metabolites were previously found by different studies investigating the biotransformation process of MON A [19,20,21], but not of MON B. Additionally, several other hydroxylated ( m/z = 709) or oxidized ( m/z = 707) TPs were known.…”

Section: Resultsmentioning

confidence: 99%

“…However, most of the studies focused on the degradation kinetics of MON and only to a lesser extent on the identification of TPs. A few studies investigated oxidative TPs, namely the conversion of MON with metalloporphyrins [28], the Jacobson catalyst [29] and the inhibition and biotransformation under different redox conditions [30].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Transformation Products of Monensin by Electrochemistry Compared to Microsomal Assay and Hydrolysis

et al. 2019

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The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation.

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Biomimetic oxidation studies of monensin A catalyzed by metalloporphyrins: Identification of hydroxyl derivative product by electrospray tandem mass spectrometry

Cited by 6 publications

References 41 publications

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

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

Identification of metabolites of anticancer candidate salinomycin using liquid chromatography coupled with quadrupole time‐of‐flight and hybrid triple quadrupole linear ion trap mass spectrometry

Prediction of Transformation Products of Monensin by Electrochemistry Compared to Microsomal Assay and Hydrolysis

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