Elucidation of DNA-Eltrombopag Binding: Electrochemical, Spectroscopic and Molecular Docking Techniques

Eltrombopag is a powerful adjuvant anticancer drug used in treating MS (myelodysplastic syndrome) and AML (acute myeloid leukemia) diseases. In this study, the interaction mechanism between eltrombopag and DNA was studied by voltammetry, spectroscopic techniques, and viscosity measurements. We developed a DNA-based biosensor and nano-biosensor using reduced graphene oxide-modified glassy carbon electrode to detect DNA-eltrombopag binding. The reduction of desoxyguanosine (dGuo) and desoxyadenosine (dAdo) oxidation signals in the presence of the drug demonstrated that a strong interaction could be established between the eltrombopag and dsDNA. The eltrombopag-DNA interaction was further investigated by UV absorption and fluorescence emission spectroscopy to gain more quantitative insight on binding. Viscosity measurements were utilized to characterize the binding mode of the drug. To shed light on the noncovalent interactions and binding mechanism of eltrombopag molecular docking and molecular dynamics (MD), simulations were performed. Through simultaneously carried out experimental and in silico studies, it was established that the eltrombopag binds onto the DNA via intercalation.

Automated summary

In this study, the interaction mechanism between Eltrombopag and DNA was investigated using voltammetry, spectroscopic techniques, and viscosity measurements. A DNA-based biosensor and nano-biosensor were developed to detect the binding of DNA and Eltrombopag. Experimental results showed that Eltrombopag strongly interacts with dsDNA, as evidenced by the reduction of dGuo and dAdo oxidation signals in the presence of the drug. UV absorption, fluorescence emission spectroscopy, and viscosity measurements were used to further characterize the binding mode of the drug. Molecular docking and molecular dynamics simulations revealed that Eltrombopag binds to DNA through intercalation.