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Development of chromatographic/electrophoretic methods to be further used in in vitro enzymatic inhibition and drug interaction of chiral pesticides

Grant number: 16/07597-0
Support type:Regular Research Grants
Duration: August 01, 2016 - July 31, 2018
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
Principal Investigator:Anderson Rodrigo Moraes de Oliveira
Grantee:Anderson Rodrigo Moraes de Oliveira
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Assoc. researchers:Norberto Peporine Lopes

Abstract

The quantification of analytes present in biological matrices requires the development of accurate and reproducible analytical methods under several conditions of analysis. Chromatographic and electrophoretic techniques (capillary electrophoresis) are techniques widely used for these purposes. These techniques have several advantages such as: simplicity, speed of the analysis and versatility. Our research group has been working on the development and validation of chromatographic and electrophoretic methods to be further applied in biotransformation and in in vitro metabolism studies of chiral drugs as well as natural products. In this new proposal, we aim to determine the enantioselectivity in in vitro metabolism of chiral agrochemicals by using human liver microsomes and further realization of enzymatic inhibition studies, phenotyping and drug interactions. These studies will be conducted with the racemic mixture as well as the pure enantiomers and the results of both studies will be compared. Our motivation for the development of this project lies in the fact that there are several enantioselective studies which evaluates the toxicity, ecotoxicity and environmental impact of the enantiomers of agrochemicals, and although the human being is in contact with these toxicants (either at work or through food intake) studies of enzymatic inhibition and drug interactions for risk assessment exposure to these products is still little carried out with human models. In this context, they will be developed and validated bioanalytical methods for this purpose. This project aims to continue the work started in the FAPESP regular projects n. 2009/06132-0; 2011/17508-1 and 2013/17658-9. (AU)

Scientific publications (10)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARTINS, JULIA; COELHO, JOANA; TADINI, MARAINE CATARINA; DE SOUZA, REBECA OLIVEIRA; FIGUEIREDO, SONIA APARECIDA; VIEIRA FONSECA, MARIA JOSE; PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; LOPES, NORBERTO PEPORINE; BERRETTA, ANDRESA; MARQUELE-OLIVEIRA, FRANCIANE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Yangambin and Epi-yangambin Isomers: New Purification Method from Ocotea fasciculata and First Cytotoxic Aspects Focusing on In Vivo Safety. Planta Medica, v. 86, n. 6, p. 415-424, APR 2020. Web of Science Citations: 0.
CARRAO, DANIEL BLASCKE; HABENCHUS, MAISA DANIELA; PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; DA SILVA, RODRIGO MOREIRA; LOPES, NORBERTO PEPORINE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. In vitro inhibition of human CYP2D6 by the chiral pesticide fipronil and its metabolite fipronil sulfone: Prediction of pesticide-drug interactions. Toxicology Letters, v. 313, p. 196-204, OCT 1 2019. Web of Science Citations: 0.
FONSECA, FRANCIELE S.; CARRAO, DANIEL B.; DE ALBUQUERQUE, NAYARA C. P.; NARDINI, VIVIANI; DIAS, LUIS G.; DA SILVA, RODRIGO M.; LOPES, NORBERTO P.; DE OLIVEIRA, ANDERSON R. M. Myclobutanil enantioselective risk assessment in humans through in vitro CYP450 reactions: Metabolism and inhibition studies. Food and Chemical Toxicology, v. 128, p. 202-211, JUN 2019. Web of Science Citations: 4.
DA SILVA, RODRIGO MOREIRA; DE GAITANI, CRISTIANE MASETTO; MAURIZ MARQUES, LUCAS MACIEL; BARACO, KARINA FRAIGE; CAVALHEIRO, ALBERTO JOSE; BERALDO DE MORAES, LUIZ ALBERTO; LOPES, NORBERTO PEPORINE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Characterization of Casearin X Metabolism by Rat and Human Liver Microsomes. Planta Medica, v. 85, n. 4, p. 282-291, MAR 2019. Web of Science Citations: 1.
CARRAO, DANIEL BLASCKE; DOS REIS GOMES, ISABEL CRISTINA; BARBOSA JUNIOR, FERNANDO; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Evaluation of the enantioselective in vitro metabolism of the chiral pesticide fipronil employing a human model: Risk assessment through in vitro-in vivo correlation and prediction of toxicokinetic parameters. Food and Chemical Toxicology, v. 123, p. 225-232, JAN 2019. Web of Science Citations: 5.
PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; CARRAO, DANIEL BLASCKE; HABENSCHUS, MAISA DANIELA; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Metabolism studies of chiral pesticides: A critical review. Journal of Pharmaceutical and Biomedical Analysis, v. 147, n. SI, p. 89-109, JAN 5 2018. Web of Science Citations: 35.
CARRAO, DANIEL BLASCKE; PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; MAURIZ MARQUES, LUCAS MACIEL; MILLER CROTTI, ANTONIO EDUARDO; PILON, ALAN CESAR; BOLZANI, VANDERLAN DA SILVA; BERRETTA, ANDRESA APARECIDA; MORAES DE OLIVEIRA, ANDERSON RODRIGO. In Vitro Metabolism of Artepillin C by Rat and Human Liver Microsomes. Planta Medica, v. 83, n. 8, p. 737-745, MAY 2017. Web of Science Citations: 4.
HABENSCHUS, MAISA DANIELA; MOREIRA, FERNANDA DE LIMA; LOPES, NORBERTO PEPORINE; DE OLIVEIRA, ANDERSON R. M. In Vitro Inhibition of Human CYP450s 1A2, 2C9, 3A4/5, 2D6 and 2E1 by Grandisin. Planta Medica, v. 83, n. 8, p. 727-736, MAY 2017. Web of Science Citations: 4.
MOREIRA, FERNANDA L.; MARQUES, LUCAS M. M.; LOPES, NORBERTO P.; DE OLIVEIRA, ANDERSON R. M. In vitro metabolism studies of natural products are crucial in the early development of medicines. PHYTOCHEMISTRY REVIEWS, v. 16, n. 2, p. 355-373, APR 2017. Web of Science Citations: 2.
PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; DE MATOS, JULIANA VICENTIN; MORAES DE OLIVEIRA, ANDERSON RODRIGO. In-line coupling of an achiral-chiral column to investigate the enantioselective in vitro metabolism of the pesticide Fenamiphos by human liver microsomes. Journal of Chromatography A, v. 1467, p. 326-334, OCT 7 2016. Web of Science Citations: 6.

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