Insight into the binding mechanism of macrolide antibiotic; erythromycin to calf thymus DNA by multispectroscopic and computational approaches

Abstract

In the present study, the interactions between Erythromycin drug and calf thymus deoxyribonucleic acid (ct-DNA) were explored by multi spectroscopic techniques (UV-Visible, fluorescence, circular dichroism spectroscopies), viscosity, molecular docking simulation, and atomic force microscopy (AFM). In addition, the values of binding constant were calculated by the UV-Visible and fluorescence spectroscopy. Competitive fluorescence study with methylene blue (MB), acridine orange (AO), and Hoechst 33258 were indicated that the Erythromycin drug could displace the DNA-bound Hoechst, which displays the strong competition of Erythromycin with Hoechst to interact with the groove binding site of DNA. In addition, the observed complexes in AFM analysis comprise the chains of ct-DNA and Erythromycin with an average size of 314.05 nm. The results of thermodynamic parameter calculations (ΔS° = −332.103 ± 14 J mol−1 K −1 and ΔH° = −115.839 ± 0.02 kJ mol−1) approved the critical role of van der Waals forces and hydrogen bonds in the complexation of Erythromycin-DNA. Fluorescence spectroscopy results demonstrate the existence of a static enhancement mechanism in the interaction of Erythromycin-DNA. According to the obtained results, Erythromycin drug interacts with the major groove of ct-DNA. These consequences were further supported by the molecular docking study, and it could be determined that DNA-Erythromycin docked model was in a rough correlation with our experimental results. Communicated by Ramaswamy H. Sarma