Abstract:
Human serum albumin (HSA) acts as a reservoir and transport protein for endogenous (e.g. fatty acids or bilirubin) and exogenous compounds (e.g. drugs or nutrients) in the blood. The binding of a drug to HSA is a major determinant of its pharmacokinetic and pharmacodynamic profile. Here, the binding interaction between homopterocarpin and HSA under simulated physiological condition was explored by fluorescence, UV–Vis spectroscopy and molecular docking. The mechanism of HSA intrinsic quenching by homopterocarpin as ligand was both collisional and static with a binding constant of 2.84 X 104 L.mol-1 at 298 K. The thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS), were calculated to be 22.46 kJmol-1 and 48.41 Jmol-1 K-1 respectively with n, the number of binding site approximately one, which indicates that 1 mole of homopterocarpin binds 1 mole of HSA via hydrophobic interaction. The positive sign for ΔG corresponds to a non-spontaneous binding process. The values of dissociation constant, Kd across the temperature of study reveals a strong affinity between HSA and homopterocarpin, thus, HSA binds homopterocarpin as a transporter reducing its free plasma concentration. In addition, the results of UV-visible, synchronous and 3-D fluorescence spectra demonstrated that the microenvironment and the native structure of HSA were changed in the presence of homopterocarpin. Moreover, the molecular docking experiment reveals homopterocarpin binds with a binding energy of -8.1 kCalmol-1 and interacts with some amino acid residues localized at Sudlow site I. The data presented can be useful in the establishment of the pharmacokinetic profiles of homopterocarpin in the process of future drug development.
