Deciphering the nature of binding of dexlansoprazole with DNA: Biophysical and docking approaches

Drugs, in general, exhibit their pharmacological activity in binding with intracellular targets. Numerous anticancer and antibacterial drugs target DNA as one of their primary intracellular targets. Dexlansoprazole (DLP) is a heterocyclic compound containing benzimidazole moiety and a proton pump inhibitor used to treat gastroesophageal reflux disease. The interaction of dexlansoprazole with calf thymus DNA (ct-DNA) has been studied using biophysical methods. The UV-Visible studies revealed a binding constant of 2.15 ± 0.3 × 104 M^-1 which is close to the value of 2.44 ± 0.3 × 10⁴ M^-1 obtained from the fluorescence studies. Competitive displacement studies using the fluorescence spectroscopic method with ethidium bromide and Hoechst as DNA markers suggested the groove binding mode of DLP in ct-DNA. The groove binding mode of DLP in ct-DNA was complemented by the results of viscosity and DNA melting studies. Further studies on the effect of ionic strength and potassium iodide on DLP binding with ct-DNA supported the observed binding mode. Circular dichroism studies reflected no significant conformational variation in ct-DNA after the interaction. The binding mode obtained from the experimental studies was corroborated by the molecular docking studies that showed the position of DLP in the minor groove of ct-DNA along with the receptor interface restudies involved in the interaction.