In vitro metabolism of monensin A: microbial and human liver microsomes models

Author(s)

Rocha, Bruno A. ^[1] ; Assis, Marilda D. ^[1] ; Peti, Ana P. F. ^[1] ; Moraes, Luiz A. B. ^[1] ; Moreira, Fernanda L. ^[2] ; Lopes, Norberto P. ^[2] ; Pospisil, Stanislav ^[3] ; Gates, Paul J. ^[4] ; de Oliveira, Anderson R. M. ^[1]

Affiliation

^[1] Univ Sao Paulo FFCLRP USP, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo FCFRP USP, Fac Ciencias Farmaceut Ribeirao Preto, Nucleo Pesquisas Prod Nat & Sintet, Ribeirao Preto - Brazil

^[3] ASCR, Inst Microbiol, Prague - Czech Republic

^[4] Univ Bristol, Sch Chem, Bristol, Avon - England

• Document type: Journal article
• Source: XENOBIOTICA; v. 44, n. 4, p. 326-335, APR 2014.
• Web of Science Citations: 8

Abstract

1. Monensin A, an important antibiotic ionophore that is primarily employed to treat coccidiosis, selectively complexes and transports sodium cations across lipid membranes and displays a variety of biological properties. 2. In this study, we evaluated the fungi Cunninghamella echinulata var. elegans ATCC 8688A, Cunninghamella elegans NRRL 1393 ATCC 10028B and human hepatic microsomes as CYP-P450 models to investigate the in vitro metabolism of monensin A and compare the products with the metabolites produced in vivo. 3. Mass spectrometry analysis of the products from these model systems revealed the formation of three metabolites: 3-O-demethyl monensin A, 12-hydroxy monensin A and 12-hydroxy-3-O-demethyl monensin A. We identified these products by tandem mass spectrometry and through comparison with the in vivo metabolites. 4. This analysis demonstrated that the model systems produce the same metabolites found in in vivo studies, thus they could be used to predict the metabolism of monensin A. Furthermore, we verified that liquid chromatography coupled to mass spectrometry is a powerful tool to study the in vitro metabolism of drugs, because it allows the successful identifications of several derivatives from different metabolic models. (AU)

• FAPESP's process: 09/51812-0 - Development of a platform for the study of in vitro and in vivo metabolism of natural products, a need for pre-clinical testing system
• Grantee: Norberto Peporine Lopes
• Support type: BIOTA-FAPESP Program - Thematic Grants
• 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: 11/17508-1 - Development and validation of chromatographic and electrophoretic methods for subsequent application in studies of in vitro metabolism and biotransformation
• Grantee: Anderson Rodrigo Moraes de Oliveira
• Support type: Regular Research Grants