In vitro-in vivo correlation of the chiral pesticide prothioconazole after interaction with human CYP450 enzymes

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorPerovani, Icaro Salgado-
Autor(es): dc.creatorSantos Barbetta, Maike Felipe-
Autor(es): dc.creatorMoreira da Silva, Rodrigo-
Autor(es): dc.creatorLopes, Norberto Peporine-
Autor(es): dc.creatorMoraes de Oliveira, Anderson Rodrigo-
Data de aceite: dc.date.accessioned2025-08-21T21:42:09Z-
Data de disponibilização: dc.date.available2025-08-21T21:42:09Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-05-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.fct.2022.112947-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/231639-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/231639-
Descrição: dc.descriptionGrowing human demand for food has culminated in increased use of pesticides worldwide. Prothioconazole (PTC), a profungicide, is bioactivated by metabolic PTC oxidation to prothioconazole-desthio (D-PTC). Here, the in vitro phase I metabolism of PTC to D-PTC in human liver microsomes and human CYP450 forms was studied. The kinetic parameters for the formation of (+)-D-PTC (KM = 1.2 μmol L−1, VMAX = 1.7 pmol min−1 mg−1), (−)-D-PTC (KM = 7 μmol L−1, VMAX = 5.1 pmol min−1 mg−1), and both D-PTC enantiomers (KM = 9 μmol L−1, VMAX = 7 pmol min−1 mg−1) from rac-PTC indicated an enantioselective behavior. Formation of the enantiomer (+)-D-PTC was twice more extensive than the formation of the enantiomer (−)-D-PTC. Furthermore, CLH prediction revealed the same enantioselective behavior. The phenotyping study indicated that CYP2C19 was the sole CYP450 form accounting for the metabolism of PTC. The estimated apparent distribution volume of PTC was predicted as 2 L kg−1. This study showed that D-PTC may be formed in the human organism due to hepatic metabolism of PTC, mediated by CYP2C19 and that the enantiomer (+)-D-PTC is preferentially formed. However, it was not extensively formed (~1%). Considering a risk assessment point of view, this study provided positive evidence of PTC safety.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionDepartamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo, SP-
Descrição: dc.descriptionNúcleo de Pesquisas de Produtos Naturais e Sintéticos Departamento de Ciências Biomoleculares Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo, SP-
Descrição: dc.descriptionNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT–DATREM) Unesp Institute of Chemistry, P.O. Box 355, SP-
Descrição: dc.descriptionNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT–DATREM) Unesp Institute of Chemistry, P.O. Box 355, SP-
Descrição: dc.descriptionFAPESP: 2014/50945-4-
Descrição: dc.descriptionFAPESP: 2016/14668-7-
Descrição: dc.descriptionFAPESP: 2018/07534-4-
Descrição: dc.descriptionFAPESP: 2020/02139-0-
Descrição: dc.descriptionFAPESP: 2021/10098-4-
Descrição: dc.descriptionCNPq: 465571/2014-0-
Idioma: dc.languageen-
Relação: dc.relationFood and Chemical Toxicology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectChiral pesticide-
Palavras-chave: dc.subjectEnantioselective-
Palavras-chave: dc.subjectHuman liver microsomes-
Palavras-chave: dc.subjectIn vitro-in vivo-
Palavras-chave: dc.subjectMetabolism-
Palavras-chave: dc.subjectProthioconazole-
Título: dc.titleIn vitro-in vivo correlation of the chiral pesticide prothioconazole after interaction with human CYP450 enzymes-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

Não existem arquivos associados a este item.