Exploring the interaction of guanidine ligands Amiloride, Rimeporide and Cariporide with DNA for understanding their role as inhibitors of Na+/H+ exchangers (NHEs): A spectroscopic and molecular docking investigation.

The inhibition of Na+/H+ Exchangers (NHEs) has shown efficacy in the pathology of several diseases like tumors, cardiovascular, and neurological disorders. The role of guanidine ligands such as amiloride, cariporide, and rimeporide as NHE inhibitors is very well documented but their interaction studies with genomic DNA are still unexplored. In this study, a combination of various biophysical and molecular docking studies was employed to investigate their binding aspects.UV–Visible, fluorescence, and circular dichroism (CD) studies indicated that guanidine ligands bind to the grooves of Calf Thymus DNA (ctDNA). Fluorescence titration studies depict that amiloride binds to ctDNA with a binding constant in the order of 102 M−1 and free energy change (ΔG0) of −14.05 KJ mol−1. Competitive fluorescence studies indicated the minor groove binding property of amiloride, whereas major groove binding mode was deduced for rimeporide and cariporide. Molecular docking studies were also found to be in accordance with the experimental results, revealing the information about the binding energy of the guanidine ligand-ctDNA complex. The docked structures depicted binding energy of −6.4 kcal mol−1 for amiloride and − 6.6 kcal mol−1 for rimeporide and cariporide. Such physicochemical studies of DNA-ligand interactions may facilitate the understanding of the mechanisms of NHE inhibition. [Display omitted] • The interaction studies of guanidine ligands (amiloride, rimeporide and cariporide) with ctDNA is still unexplored. • DNA-drug interaction. • Several biophysical and molecular docking techniques are used to study DNA-guanidine ligands interaction. • Amiloride interacts with the minor groove of ctDNA • Rimeporide and cariporide both interact with the major groove of ctDNA. [ABSTRACT FROM AUTHOR]