Interaction of a Third-Generation Tyrosine Kinase Inhibitor with dsDNA: Electrochemical and Spectroscopic Studies

Abstract

In the current study, an evaluation was conducted regarding potential interaction mechanisms occurring between ponatinib (Pntb), a tyrosine kinase inhibitor of third-generation and double-stranded deoxyribonucleic acid (dsDNA). The aim of these studies was to elucidate the mechanism underlying the interaction between Pntb and DNA. This understanding could not only shed light on the changes occurring within living organisms but also, in the future, facilitate the development of new drugs for cancer treatment and improve their therapeutic effectiveness. The interactions were examined using square wave voltammetry (SWV) and UV-Vis spectroscopy. In order to conduct voltammetric experiments, a glassy carbon electrode was used. The addition of dsDNA to ponatinib solution resulted in a decrease of current peaks of the latter and resulted in a positive peak potential shift, suggesting that the intercalative type of interaction is the most likely to occur. Studies with utilization of UV-Vis spectroscopy have revealed a hypochromic effect, resulting in lack of wavelength shift in absorption maximum, following the addition of DNA to ponatinib solution, and confirming that intercalation is the predominant interaction between Pntb and dsDNA. The calculated value of the binding constant for Pntb-dsDNA determined by SWV was equal to 1.71 x 107 M-1. The values calculated from UV-Vis spectroscopy, however, were 1.13 x 107 M-1.