Exploring the toxicity of fluoxastrobin: a combined computational and experimental approach

Fluoxastrobin (FLUO) is a fungicide from strobilurin family used widely worldwide. The use of FLUO pesticide is on the rise and this phenomenon is accompanied by a series of concerns such as endocrine disruption. In order to determine the potential toxic effects of FLUO, cell culture, gene expression and molecular docking assays were conducted as it is crucial to determine the interaction between chemicals and nuclear receptors in order to estimate and understand the impact of the chemical. This study analyzed the quantum properties of FLUO at the molecular quantum mechanical level using Density Functional Theory (DFT) with the B3LYP/6-311 + + G(d, p) and cc-pVDZ basis sets including the HOMO-LUMO energy gap, chemical reactivity descriptors, molecular electrostatic potential (MEP) surface calculation. In order to investigate molecular characteristics, topological (AIM, RDG) and Natural Bonding Orbitals (NBO) investigations were conducted. Molecular docking studies were performed with the title compound in the active sites of the proteins selected because of their role in xenobiotic metabolism. The docking result was determined to be a significant factor in bioactivity, a finding that is corroborated by the cytotoxic analysis of the FLUO compound. Density Functional Theory (DFT) computations are used to support molecular docking analysis. Toxicity of FLUO was tested on MDA-MB-231 cells using XTT and wound healing assays. IC50 value of FLUO was determined as 6,9 µg/ml. The impact of FLUO exposure at molecular level was assessed using qRT-PCR by determining the expression levels of PPARy, AhR and PXR genes where no statistically significant change was found.