Minor groove binding of antihistamine drug bilastine with calf thymus DNA: A molecular perspective with thermodynamics using experimental and theoretical methods

Molecular recognition which are driven by molecular interactions, is of great interest in drug discovery and targeted drug delivery systems since drugs exhibit their medicinal characteristics when it interacts with target biomolecules. Deoxyribose nucleic acid (DNA) is one of the primary targets for many therapeutic drugs and understanding them at the molecular level is at the forefront of active research. Bilastine (BLS) is one of the commercially available heterocyclic compounds with a benzimidazole nucleus used in the treatment of chronic urticaria and recurrent allergic rhinoconjunctivitis. Various biophysical methods have been employed for the investigation of binding interaction studies between BLS and ct-DNA. UV-Visible and fluorescence spectral studies revealed the interaction between BLS and DNA. UV-Visible studies suggested a binding constant of 1.17 +/- 0.2 x105 M-1. ct-DNA quenched the fluorescence of BLS, and the quenching was found to involve static and dynamic processes. From fluorescence studies, the binding constants were found to be 1.17 +/- 0.2x105, 1.65 +/- 0.3x105, 2.01 +/- 0.3x105 at 298, 303, and 308 K respectively. The interaction was spontaneous in nature with negative Delta G0 values and hydrophobic force was the major driving force with positive Delta H0 (41.54 +/- 2.5KJ mol-1) and Delta S0 (236.63 +/- 3.1J mol-1 K-1) values. Site marker displacement using ethidium bromide, and Hoechst along with viscosity measurement, DNA melting studies confirmed the binding of BLS in the minor-groove of ct-DNA. The minor-groove binding was further supported by studies with KI. Effect of NaCl on the binding revealed an insignificant role of electrostatic interactions. DNA conformational changes were not observed from circular dichroism (CD) studies. Molecular docking studies corroborated the experimental results showing the location of BLS in the minor groove of ct-DNA.