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 anti-cancer 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 gastro-esophageal 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 x 10(4 )M(-1) which is close to the value of 2.44 +/- 0.3 x 10(4) M-1 obtained from the fluorescence studies. Competitive displacement studies using the fluorescence spectroscopic method with ethidium bromide and Hoechst as DNA markers sug-gested the groove binding mode of DLP in ct-DNA. The groove binding mode of DLP in ct-DNA was com-plemented 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.

Automated summary

Drugs generally exert their pharmacological activity by binding with intracellular targets, and this study focuses on the interaction between DLP and DNA. Using various biophysical methods, it was found that DLP interacts with ct-DNA in a groove binding mode, which was supported by experimental evidence and molecular docking studies.