In vitro evaluation of the inhibitory potential of chiral pesticide penconazole on the main Cytochrome P450 enzymes involved in drugs metabolism

• Grant number: 20/02826-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2020
• End date: June 30, 2021
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Anderson Rodrigo Moraes de Oliveira
• Grantee: Lizandra Bruna Simões de Oliveira
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Penconazole (PEN) is a chiral fungicide used mainly in grape crops against powdery mildew and rust disease. In a chiral environment, such biomolecules, enantiomers can interact differently leading to differences in metabolism, bioactivity and toxicity. Enantioselective studies involving PEN have already reported differences in the activity, metabolism and toxicity of its enantiomers. In addition, some studies have reported the presence of this pesticide and its metabolites in the urine of agricultural workers, thus showing the population's exposure to this pesticide. Due to the great exposure of the human population, mainly the elderly, to medications, drug interactions and possible toxic effects may occur. Given this fact and the lack of information about the effect of this pesticide on humans, this project aims to evaluate in vitro the ability of PEN (in the form of racemic mixture and with isolated enantiomers) to inhibit the main cytochrome P450 isoforms of involved in drug metabolism. This study will allow to predict possible drug-pesticide interactions and will provide society with more information about the safety of pesticide use.