Evaluation of the interaction mechanism of dsDNA-propofol binding: Electrochemical, thermodynamic, molecular docking studies and comet assay

Abstract

Propofol, a widely used intravenous hypnotic agent, is favored in medical settings due to its rapid onset and short duration of action. This study systematically assessed the interaction between propofol and DNA using voltammetry, fluorescence spectroscopy, molecular docking, and comet assay analysis. The voltammetric peak responses for dGuo and dAdo on the ct-dsDNA biosensor were detected at 0.96 V and 1.23 V, respectively. 4 × 10⁻⁷ mol L⁻¹ propofol at 300 s were selected as optimal interaction concentration, which significantly reduced the peak currents of dsDNA signals. In the incubation solution, a significant decrease in the peak currents of both dGuo and dAdo was observed in the 1 × 10⁻⁴ mol/L propofol. To analyze the quenching mechanism, experiments were conducted at various temperatures with Stern-Volmer plots using the fluorescence titration method. The decrease in Ksv values as temperature increases suggests an involvement of static quenching. ΔH° < 0 and ΔS° < 0 indicate the hydrogen bonds and van der Waals interactions; ΔG° < 0 and Kb value of 1.26 × 10⁶ L.mol⁻¹ demonstrate spontaneous interactions between propofol and DNA. Iodide quenching studies revealed that propofol may interact with dsDNA by groove binding. In the comet assay, the highest level of DNA damage was observed at 200 μg/ml propofol concentration. In silico studies, it has been supported that propofol binds to specific minor regions on DNA, forming van der Waals interactions.