Kolaviron influences calf thymus DNA conformational stability and structural dynamics: a multi-spectroscopic and molecular dynamics analysis.

Kolaviron, flaunted for its anticancer potential, has driven our exploration of its mechanism of interaction with DNA, and further shedding light on its therapeutic promise. Herein, the binding efficacy and thermodynamics of kolaflavanone, a component of kolaviron, with double-stranded calf thymus DNA (ctDNA), were investigated using a range of spectroscopic techniques and molecular docking simulations. Syllogistically, spectroscopic techniques, viscometric analysis, and thermal denaturation revealed that kolaflavanone binds to the double-stranded ctDNA minor groove via electrostatic interactions, with binding constants of 105 L·mol-1. The interaction was both enthalpically and entropically driven, with a ΔH value of -18.16 kJ/mol and a ΔS value of 38.60 J/mol/K at 25 °C. This resulted in subtle but negligible structural perturbations of the ctDNA native B-conformation. ctDNA has one binding site for the flavonoid. Molecular docking and dynamics simulation analyses confirmed that kolaflavanone binds to the minor groove of DNA with a preference for the A-T region and a binding affinity of -7.4 kcal/mol. The conjugate's stability, conferred by minor groove binding and non-intercalative interactions, suggests a promising strategy for designing DNA-targeted therapeutics with enhanced stability and tumor-specific gene regulation potential.