Multi-spectroscopic and molecular modelling studies on the interaction of esculetin with calf thymus DNA

Abstract

Understanding the interaction of small molecules with DNA has become an active research area at the interface between chemistry, molecular biology and medicine. Plant derived polyphenols possess diverse biological and pharmacological properties. Esculetin is a coumarin derivative polyphenolic compound having diverse pharmacological and therapeutic properties. However, its mode of interaction with DNA is still not well understood. In the present study, we have attempted to determine the mode of binding of esculetin with calf thymus DNA (Ct-DNA) through various biophysical techniques. Analysis of UV-visible absorbance spectra and fluorescence spectra indicates the formation of a complex between esculetin and Ct-DNA. The binding constant was found to be 1.87 × 10(4) M(-1). Thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures indicated that hydrophobic interactions and hydrogen bonding played major roles in the binding process. Several other experiments such as iodide induced quenching and competitive displacement studies with ethidium bromide, acridine orange and Hoechst 33258 suggested that esculetin possibly binds to the minor groove of the Ct-DNA. The strong dependence on ionic strength in controlling the binding of esculetin with Ct-DNA confirms the possibility of electrostatic interaction. These observations were further supported by DNA melting studies, viscosity measurements, CD spectral analysis and in silico molecular docking.

Studying non-covalent drug–DNA interactions

“…It is also possible to calculate the intrinsic binding constant from these fluorescence quenching experiments by using the following equation [24], Fluorescence spectroscopy is often used to determine the binding mode of drugs with DNA by utilising various analytical tools that are based on the fluorescence emission property of the drug. Fluorescence titration of small molecule in presence of ssDNA and dsDNA is done to elucidate the binding mode of these small molecules with DNA (Fig.…”

DNA interaction and cytotoxic activity of copper complex based on tridentate hydrazone derived ligand and nitrogen donor heterocycle

“…Positive ΔS value, 7.96 cal/mol/K suggests the involvement of hydrophobic interactions. Thus, complex binds to DNA through hydrogen bonding as well as hydrophobic interactions [38].The interaction of the complex with the DNA through hydrogen bond is supported by molecular docking studies. Complex was docked using DNA (PDB ID: 2D55) and was found to get intercalated in the base pairs (Fig.…”

“…Positive ΔS value, 7.96 cal/mol/K suggests the involvement of hydrophobic interactions. Thus, complex binds to DNA through hydrogen bonding as well as hydrophobic interactions [38].…”

“…3) was carried out at different temperatures [37,38]. A linear Stern-Volmer graph was plotted and K sv values were calculated.…”

“…In order to understand the forces involved in the interactions, an acridine orange fluorescence displacement assay (Fig. 3) was carried out at different temperatures [37,38]. A linear Stern-Volmer graph was plotted and K sv values were calculated.…”