Multi‐spectroscopic, thermodynamic and molecular docking studies to investigate the interaction of eplerenone with human serum albumin

Abstract

The binding of small molecular drugs with human serum albumin (HSA) has a crucial influence on their pharmacokinetics. The binding interaction between the antihypertensive eplerenone (EPL) and HSA was investigated using multi-spectroscopic techniques for the first time. These techniques include ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR), native fluorescence spectroscopy, synchronous fluorescence spectroscopy and molecular docking approach. The fluorescence spectroscopic study showed that EPL quenched HSA inherent fluorescence.The mechanism for quenching of HSA by EPL has been determined to be static in nature and confirmed by UV absorption and fluorescence spectroscopy. The modified Stern-Volmer equation was used to estimate the binding constant (K b ) as well as the number of bindings (n). The results indicated that the binding occurs at a single site (K b = 2.238 Â 10 3 L mol À1 at 298 K). The enthalpy and entropy changes (ΔH and ΔS) were 58.061 and 0.258 K J mol À1 , respectively, illustrating that the principal intermolecular interactions stabilizing the EPL-HSA system are hydrophobic forces.Synchronous fluorescence spectroscopy revealed that EPL binding to HSA occurred around the tyrosine (Tyr) residue and this agreed with the molecular docking study.The Förster resonance energy transfer (FRET) analysis confirmed the static quenching mechanism. The esterase enzyme activity of HSA was also evaluated showing its decrease in the presence of EPL. Furthermore, docking analysis and sitespecific markers experiment revealed that EPL binds with HSA at subdomain IB (site III).

Interactions between hydroxylated polycyclic aromatic hydrocarbons and serum albumins: multispectral and molecular docking analyses

“…[ 17 ] These structural variations cause significant differences in the pharmacological and biochemical properties of the two proteins. [ 18,19 ] Previous studies have revealed that the binding ability of HSA with ligands, such as drugs [ 17,20,21 ] and dyes, [ 22,23 ] is different to that of BSA. The binding of xenobiotic pollutants to functional biomacromolecules is considered as the origin of their toxic effects.…”