Investigation of the interaction between anticancer drug ibrutinib and double-stranded DNA by electrochemical and molecular docking techniques

Abstract

Ibrutinib is Bruton’s tyrosine kinase inhibitor that is generally used in the treatment of lymphoma. The investigation of anticancer drug - double-stranded DNA (dsDNA) interaction is a key issue for cancer treatment. In this study, electrochemical and molecular docking studies were realized to explain the interaction mechanism between ibrutinib and dsDNA. Two interaction methods, including DNA biosensors and incubated solutions, were used in voltammetric studies. The interaction was evaluated based on the voltammetric responses of desoxyguanosine and desoxyadenosine by differential pulse voltammetry in pH 4.70 acetate buffer. The influence of accumulation concentration and time of ibrutinib on the voltammetric responses of these electroactive dsDNA bases were performed. At dsDNA biosensor, the reproducibility results (RSD%) of peak currents of desoxyguanosine and desoxyadenosine were found as 1.95 and 1.74, respectively. The dsDNA biosensor was kept in the range of 2.0 – 20.0 µM of IBR solutions for 5 min. A molecular docking study revealed that binding an ibrutinib molecule with dsDNA suggests a groove-binding mode of interaction, and the dominating interaction force is hydrogen bonding.