Spectro-thermodynamics and molecular docking analysis of abiraterone and its binding to calf thymus DNA

摘要: Binding of toxic ligands to DNA could result in undesirable biological processes, such as carcinogenesis or mutagenesis. Binding mode of abiraterone, a steroid drug and CT-DNA (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 abiraterone and CT-DNA were explored through spectroscopic and molecular docking studies. The results indicated the binding of abiraterone to CT-DNA in the minor groove. The binding constants were in the range of 1.35× 10 6–0.36× 10 6 L mol-1 at the studied temperatures. Fluorescence and spectrophotometric data suggested static quenching between CT-DNA and abiraterone The endothermic values of thermodynamic parameters ΔH=-82.8 kJ mol− 1; ΔS=-161 J mol− 1 K− 1 suggested that hydrogen bondinging is the main force involved in binding CT-DNA and abiraterone. In experimental studies the free binding energy at 298K was− 34.9 kJ mol− 1 with the relative binding energy≈− 29.65 kJ mol− 1 of docked structure. The Ksv obtained for abiraterone-KI was similar to that for abiraterone-CT-DNA-KI demonstrating no protection by CT-DNA against quenching effect of KI. Thus, suggesting involvement of groove binding between abiraterone and CT-DNA. No change in the fluorescence intensity of abiraterone-CT-DNA 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 abiraterone.