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 multispectroscopic, 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.
Analysis of the Interaction of Dp44mT with Human Serum Albumin and Calf Thymus DNA Using Molecular Docking and Spectroscopic Techniques
