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

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 x 10(3) L mol(-1)at 298 K). The enthalpy and entropy changes ( increment H and increment S) were 58.061 and 0.258 K J mol(-1), 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 Forster 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 site-specific markers experiment revealed that EPL binds with HSA at subdomain IB (site III).

Automated summary

This study investigated the binding interaction between the antihypertensive drug eplerenone and human serum albumin (HSA) using various spectroscopic techniques. The results showed that the binding between eplerenone and HSA is static in nature and is primarily stabilized by hydrophobic forces. Eplerenone was found to bind to the tyrosine residue of HSA. Moreover, the study also revealed a decrease in esterase enzyme activity of HSA in the presence of eplerenone.