Salmon Sperm DNA Binding Study to Cabozantinib, a Tyrosine Kinase Inhibitor: Multi-spectroscopic and Molecular Docking Approaches

In the current work, the binding interaction of cabozantinib with salmon sperm DNA (SS-DNA) was studied under simulated physiological conditions (pH 7.4) using fluorescence emission spectroscopy, UV-Vis absorption spectroscopy, viscosity measurement, ionic strength measurement, FT-IR spectroscopy, and molecular modeling methods. The obtained experimental data demonstrated an apparent binding interaction of cabozantinib with SS-DNA. The binding constant (K) of cabozantinib with SS-DNA evaluated from the Benesi-Hildebrand plot was equal to 5.79 × 10 at 298 K. The entropy and enthalpy changes (∆S and ∆H) in the binding interaction of SS-DNA with cabozantinib were 44.13 J mol K and -19.72 KJ mol, respectively, demonstrating that the basic binding interaction forces are hydrophobic and hydrogen bonding interactions. Results from UV-Vis absorption spectroscopy, competitive binding interaction with rhodamine B or ethidium bromide, and viscosity measurements revealed that cabozantinib binds to SS-DNA via minor groove binding. The molecular docking results revealed that cabozantinib fits into the AT-rich region of the B-DNA minor groove and the binding site of cabozantinib was 4 base pairs long. Moreover, cabozantinib has eight active torsions, implying a high degree of flexibility in its structure, which played a significant role in the formation of a stable cabozantinib-DNA complex.