Electrochemical and theoretical study on interaction between erlotinib and DNA

A comprehensive investigation of tyrosine kinase inhibitor erlotinib (ERL) electrochemical behavior and interaction with DNA was performed with the aim to clarify its redox mechanism and to determine the mode of binding. Irreversible oxidation and reduction processes of ERL on glassy carbon electrode were investigated using three voltammetric techniques CV, DPV, SWV in pH range between 2.0 and 9.0. Oxidation was established as an adsorption-controlled process, while the reduction manifested diffusion-adsorption mixed controlled process in acidic medium and adsorption became predominant in the neutral solutions. According to the determined number of transferred electrons and protons, oxidation and reduction mechanism of ERL are proposed. To follow the interaction between ERL and DNA, the multilayer ct-DNA electrochemical biosensor was incubated in ERL solutions concentrations ranged from 2 × 10–7 M to 5 × 10–5 M (pH 4.6) for 30 min. SWV measurements have shown the decrease in deoxyadenosine peak current as a consequence of ERL increased concentration and binding to ct-DNA. The calculated value of binding constant was K = 8.25 × 104 M−1. Molecular docking showed that ERL forms hydrophobic interactions when docked into minor groove, as well as when intercalated, and molecular dynamics analysis predicted the stability of obtained complexes. These results together with voltammetric studies imply that the intercalation could be more dominant way ERL binding to DNA compared to minor groove binding. •New data regarding the Erlotinib (ERL) oxidation and reduction mechanism.•Investigation of ERL ̶ DNA interaction using a multilayer biosensor and SWV.•The calculated binding constant of the complex K = 8.25 × 104 M−1.•ERL ̶ DNA binding modes: intercalation and groove binding.•Stability of intercalation complexes predicted by molecular dynamics simulations analysis.