Electrochemical Analysis of the Interaction between DNA and Abiraterone D4A Metabolite

The electroanalytical characteristics of double-stranded DNA (dsDNA) and the complex of dsDNA with the anticancer drug metabolite, abiraterone D4A, in the concentration range of 25–200 μM were investigated using differential pulse voltammetry. The effect of D4A on dsDNA was detected by changes in the intensity of the electrochemical oxidation of the heterocyclic bases guanine, adenine, and thymine. This investigation used screen-printed electrodes modified with carbon nanotubes. Binding constants ( K b ) for guanine, adenine, and thymine in the dsDNA/D4A complexes were calculated to be 1.1 × 10 4 , 5.5 × 10 3 , and 2.5 × 10 3 M –1 , respectively. The DNA-mediated electrochemical coefficients of the toxic effect were calculated as the ratio of the signal intensities of guanine and adenine in the presence of D4A compared to those without the drug ( T , %). Based on an analysis of electrochemical parameters and binding constant values, an assumption was made regarding the mechanism of the interaction between D4A and DNA, predominantly through electrostatic interactions and the formation of hydrogen bonds with the minor groove. Conclusions about the mechanism of the interaction of the abiraterone D4A metabolite with the dsDNA minor groove, obtained by electrochemical methods, were supported by the molecular simulation of the DNA/D4A complex.