In vitro enantioselective evaluation of the effect of chiral pesticides on main human cytochrome P450 enzymes involved in drug metabolism: in vitro-in vivo correlation and prediction of pesticide-drug interaction

• Grant number: 21/10098-4
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2022 - January 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Anderson Rodrigo Moraes de Oliveira
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In this new proposal, we aim to continue the project started previously (FAPESP 2018-07534-4) whose validity ended on 03/31/2021. The main objective of this project is the in vitro determination of enantioselectivity in the metabolism and enzymatic inhibition of chiral pesticides on the main cytochrome P450 (CYP450) enzymes involved in drug metabolism. These studies will be conducted with the racemic mixture and with the isolated enantiomers and the results of both studies will be compared. The kinetic data generated (KM, VMAX, Ki) allow the subsequent realization of the in vitro-in vivo correlation and prediction of drug interactions, thus aiding in the risk assessment of the evaluated pesticides. Our motivation for continuing this project lies in the fact that the studies we carried out with the pesticides fenamiphos, myclobutanil, fipronil, ethofumesate and tebuconazol indicated an important participation of CYP450 enzymes in the metabolism of these agrochemicals and a high inhibition potential. Although there are enantioselective studies that assess the toxicity, ecotoxicity and environmental impact of pesticide enantiomers, and although humans are in contact with these molecules (whether during work or through ingestion of contaminated food or water) inhibition studies enzymatic and prediction of drug interactions to assess the risk of exposure to these products is not still being performed by using human models. In this sense, our research group was a pioneer in these studies. Therefore, in this new proposal described in the next paragraphs, we will focus our studies on the analysis of the chiral pesticides prothioconazole, acephate, methamidophos, penconazole and imazamox, which are widely used in agriculture. (AU)

Scientific publications

(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)

BARBETTA, MAIKE FELIPE SANTOS; PEROVANI, ICARO SALGADO; DUARTE, LEANDRO OKA; DE OLIVEIRA, ANDERSON RODRIGO MORAES. Enantioselective in vitro metabolism of the herbicide diclofop-methyl: Prediction of toxicokinetic parameters and reaction phenotyping. Journal of Pharmaceutical and Biomedical Analysis, v. 235, p. 9-pg., 2023-10-25. (18/07534-4, 14/50945-4, 21/10098-4)

PEROVANI, ICARO SALGADO; SANTOS BARBETTA, MAIKE FELIPE; DA SILVA, RODRIGO MOREIRA; LOPES, NORBERTO PEPORINE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. In vitro-in vivo correlation of the chiral pesticide prothioconazole after interaction with human CYP450 enzymes. Food and Chemical Toxicology, v. 163, p. 8-pg., 2022-03-22. (21/10098-4, 20/02139-0, 14/50945-4)