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

Anna Tanuja Safala Bodapati, Bijaya Ketan Sahoo, Srinivas Reddy Ragaiahgari, Lavanya Kandikonda, Shravya Rao Madku

Journal: International journal of biological macromolecules 2022;217():1027-1036

PMID: 35907469

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Abstract

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 which is close to the value of 2.44 ± 0.3 × 10 M 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.

Address: Chemistry Division, BS&H Department, BVRIT Hyderabad, College of Engineering for Women, Hyderabad 500090, India; Department of Chemistry, GITAM Deemed to be University, Hyderabad Campus 502329, India.; Department of Chemistry, GITAM Deemed to be University, Hyderabad Campus 502329, India. Electronic address: [email protected].; Department of Chemistry, GITAM Deemed to be University, Hyderabad Campus 502329, India; Department of Chemistry, B V Raju Institute of Technology (BVRIT), Narsapur 502313, India.; Department of Chemistry, GITAM Deemed to be University, Hyderabad Campus 502329, India; Department of Chemistry, Gokaraju Rangaraju Institute of Engineering and Technology, Hyderabad 500090, India.; Department of Chemistry, GITAM Deemed to be University, Hyderabad Campus 502329, India; Department of Chemistry, St. Francis College for Women, Hyderabad 500016, India.

DOI: 10.1016/j.ijbiomac.2022.07.177

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MeSH Terms: Circular Dichroism, DNA, Dexlansoprazole, Molecular Docking Simulation, Nucleic Acid Conformation, Nucleic Acid Denaturation, Spectrometry, Fluorescence, Spectrophotometry, Ultraviolet, Thermodynamics, Viscosity