Spectro-thermodynamics and molecular docking analysis of abiraterone and its binding to calf thymus DNA
Binding of toxic ligands to DNA could result in undesirable biological processes, such as carcinogenesis or mutagenesis. Binding mode of Abiraterone (ABR), a steroid drug and ctDNA(calf thymus DNA was investigated in this study using fluorescence and ultraviolet-visible spectroscopy. The probable prediction of binding and the type of interaction forces involved in the arrangement between ABR and ctDNA were explored through spectroscopic and molecular docking studies. The results indicated the binding of ABR to ctDNA in the minor groove. The binding constants were in the range of 1.35 x 106 - 0.36x 106 L mol-1 at the studied temperatures. Fluorescence and spectrophotometric data suggested static quenching between ctDNA and ABR The endothermic values of thermodynamic parameters {Delta}H = -82.8 kJ mol-1; {Delta}S = - 161 J mol-1 K-1 suggested that hydrogen bonding is the main force involved in binding ctDNA and ABR. In experimental studies the free binding energy at 298K was -34.9 kJ mol-1 with the relative binding energy {approx} -29.65 kJ mol-1 of docked structure. The Ksv obtained for ABR-KI was similar to that for ABR-ctDNA -KI demonstrating no protection by ctDNA against quenching effect of KI. Thus, suggesting involvement of groove binding between ABR and ctDNA. No change in the fluorescence intensity of ABR-ctDNA was observed in presence of NaCl. Thus, ruling out the involvement of electrostatic interaction. These studies could serve as new insights in understanding the mechanisms of toxicity, resistance and side effects of ABR.