Biological and computational evidence of dinotefuran–DNA interactions: A combined in vitro and in silico study

Abstract

The potential of the neonicotinoid insecticide dinotefuran to induce oxidative DNA damage was evaluated in human peripheral blood lymphocyte cultures at three concentrations (0.05, 0.15, and 0.30 µg/mL) using the single-cell gel electrophoresis assay (COMET). Its ability to interact with DNA was further examined through molecular docking analysis. The comet assay results revealed statistically significant increases (p < 0.001) in both the genetic damage index (GDI) and the percentage of heavily damaged cells (DCP) at all tested concentrations compared with the negative control. DNA damage within individual cells caused by genotoxic agents can thus be effectively detected using the comet assay, as demonstrated in our study. Additionally, the optimized molecular structure, total energy, molecular orbital energies, molecular electrostatic potential (MEP) maps, and global reactivity parameters of dinotefuran were obtained using the DFT/B3LYP/6-311G(d,p) method. The fully optimized energy was predicted, and geometric parameters were compared with available single-crystal structure data. Computational studies employing density functional theory (DFT) and MEP analyses provided detailed insights into the geometric and electronic characteristics of dinotefuran, suggesting that the compound possesses significant chemical reactivity and potential for biological activity upon interaction with DNA. Molecular docking studies with the B-DNA dodecamer (PDB ID: 1BNA) yielded a minimum binding energy of −6.24 kcal/mol. Dinotefuran was found to form four conventional hydrogen bonds, two carbon-hydrogen bonds, and one π-donor hydrogen bond with DNA, primarily involving guanosine, cytosine, and thymidine bases. These interactions are consistent with the experimental evidence of genetic-oxidative DNA damage, indicating that dinotefuran can establish strong molecular interactions with DNA.

Graphical Abstract