Multi-spectroscopic and in silico investigation of gambogic acid-calf thymus DNA interactions

Gambogic acid (GA), a xanthanoid compound, is derived from Garcinia Hanbury gamboge resin. Studying GA's DNA binding and targeting processes is crucial to understanding its tumor-targeting potentiality. This study used spectroscopic and in silico methods to investigate the GA-calf thymus DNA-binding interaction. The results of the UV-visible absorbance spectroscopy revealed that GA binds to DNA and forms a complex. Investigation of fluorescence quenching using ethidium bromide-DNA revealed that GA displaced ethidium bromide, and the type of quenching was static in nature, as determined by Stern-Volmer plot data. Thermodynamic analysis of the DNA-GA complex revealed a spontaneous, favorable interaction involving hydrogen bonding and hydrophobic interactions. Quenching experiments with potassium iodide, Acridine orange, and NaCl verified GA's groove-binding nature and the presence of weak electrostatic interactions. The thermal melting temperature of DNA in its native and bound states with GA did not differ significantly (69.27° C to 71.25° C), validating the binding of GA to the groove region. Furthermore, the groove-binding nature of GA was confirmed by studying its interaction with ssDNA and DNA viscosity. The methods of DSC, FT-IR, and CD spectroscopy have not revealed any structural aberrations in DNA bound with GA. Molecular docking and modeling studies revealed that GA has a groove-binding nature with DNA, which is consistent with prior experimental results. Finally, the findings shed information by which GA attaches to DNA and provide insights into its recognized anticancer effects via topoisomerase inhibition causing DNA cleavage, inhibition of cell proliferation and apoptosis.