Fluorometric and molecular docking investigation on the binding characteristics of SB202190 to human serum albumin

The interaction of SB202190, a p38 mitogen-activated protein kinase inhibitor with the main drug transporter in human circulation, human serum albumin (HSA) was studied using fluorescence spectroscopy and in silico docking methods. The association constant, Ka of the binding reaction was determined to be 3.24±0.07×104 M−1 at 25 °C based on fluorescence quenching titration results. The values of enthalpy change and entropy change for the interaction were found as −8.54 kJ mol−1 and 58.01 J mol−1 K−1, respectively. Both thermodynamic data and docking results suggested the involvement of hydrophobic and van der Waals forces in the complex formation. Three-dimensional fluorescence data of SB202190-HSA complex demonstrated significant changes in the microenvironment around the protein fluorophores upon drug binding. Comparison of HSA thermograms obtained in the absence and the presence of SB202190 suggested improved protein thermal stability upon complexation with the drug. Competitive drug displacement results as well as modeling data concluded the preferred binding site of SB202190 on HSA as Sudlow׳s site I.