Background: Interactions of drugs with DNA and proteins may modify their biological
activities and conformations, which effect transport and biological metabolism of drugs.
Objective: In this study the interaction of anticancer drug regorafenib (REG) with calf thymus-DNA
(ct-DNA) and human serum albumin (HSA) has been investigated
Methods: Hence, for the first time, it was discovered interaction between REG with DNA and
HSA using multi-spectroscopic, zeta potential measurements and molecular docking method.
Results and Discussion: DNA displacement studies showed that REG does not have any effect on
acridine orange and methylene blue bound DNA, though it was substantiated by displacement
studies with Hoechst (as groove binder). Furthermore, the different concentrations of REG induce
slight changes in the viscosity of ct-DNA. Zeta potential parameters indicated that hydrophobic interaction
plays a major role in the DNA-REG complex. Results obtained from molecular docking
demonstrate that the REG prefers to bind on the minor groove of DNAs than that of the major
groove. Binding properties of HSA reveal that intrinsic fluorescence of HSA could be quenched by
REG in a static mode. The competitive experiments in the presence of warfarin and ibuprofen (as
site markers) suggested that the binding site of REG to HSA was most probably located in the subdomain
IIA. Measurements of the zeta potential indicated that REG bound to HSA mainly by both
electrostatic and hydrophobic interactions. It was found on docking procedures that REG could fit
well into HSA subdomain IIA, which confirmed the experimental results.
Conclusion: In conclusion, REG can be delivered by HSA in a circulatory system and affect DNA
as potential target.