Insights into dopaminergic agent cabergoline-induced DNA-destabilisation through spectroscopic, thermodynamic and molecular docking/metadynamics simulation studies.

Investigating the interaction of therapeutic drugs with DNA is crucial for assessing the possibility of drugs inducing significant DNA alterations when administered. The dopaminergic drug cabergoline's (CBG) interaction with CT-DNA was investigated using multi-spectroscopic, calorimetric, electrophoresis, and computational approaches. The UV-Vis and fluorescence spectral results certified the complexation of CBG with CT-DNA. Though competitive dye displacement assay, viscosity measurements, 1H NMR, KI, and urea studies strongly evidenced the intercalation-type binding mode of CBG, the molecular docking studies disclosed CBG as a groove binder as well as a partial intercalator in the minor and major grooves of DNA, respectively. The significant distortions in the characteristic CD bands of CT-DNA and the results of GEL electrophoresis evidenced the DNA-destabilizing nature of CBG. The profound decrease of 7.3 °C in the Tm of CT-DNA in the presence of CBG reiterated CBG as a DNA destabiliser. The results of metadynamics simulation and binding studies of CBG with single-strand DNA showed that the high affinity of CBG towards ssDNA compared to the dsDNA triggered CBG to destabilise dsDNA. Interestingly, the three different thermodynamic parameters resulted in the calorimetric titration of CBG with CT-DNA, exposing the sequential binding pattern involved in the CBG/CT-DNA complexation and proposing the plausible mechanism of CBG-induced DNA destabilisation.