Exploration of DNA binding mode of Coumarin Glycoside Esculin by Multispectral and Molecular dynamics approaches

Abstract

Due to the unwanted and undesired effects of existing anticancer agents, medicinal chemists are exploring drugs from natural origin. Phytochemicals and their derivatives can be developed as Biologically diverse agents with fewer side effects. Therefore, exploration of the different biological activities of natural products had been a keen interest in repurposing of the drugs. Present study focuses on the analysis of DNA (Deoxyribonucleic Acid) interactions of esculin using spectroscopic and molecular docking, simulation techniques, and MMGBSA (Molecular Mechanics Generalizing Born Surface Area) calculations. We used different spectral techniques to investigate the interactions of esculin with DNA. FTIR (Fourier Transform Infra Red Spectroscopy) spectral studies suggested the primary formation of non-covalent bond between esculin and the nitrogen base of DNA, stating the primary analysis of interactions. The observation revealed that the UV-visible (UltraViolet) spectra of esculin exhibited perturbations in the presence of CT (Calf thymus) DNA and interacted with DNA in the groove binding mode. The hyperchromic effect was determined by the increase in the absorbance value of esculin in the presence of DNA, and the binding constant (K_b) value of esculin was 2.327 ± 0.09 × 10³ M^-1. By conducting circular dichroism and viscometric analysis of DNA in the presence of esculin, we could support the groove binding mode of esculin. In Silico studies suggested that esculin has bound in the major groove between the base pairs with 6 Hydrogen bond interactions with different nucleobases. Molecular simulation analysis supported the results with lowest RMSD (Root mean square deviation), stating the stable complex of PDB (Protein Data Base) and esculin. MMGBSA analysis suggested that significant contributions from van der Waals interactions made the overall binding favorable. These findings can lead to design of DNA interacting esculin based derivatives exhibiting the anticancer potential.