Biophysical and computational view on the in vitro combination between an anticancer drug, saracatinib and human serum albumin

Abstract

Interaction behaviour of an anticancer drug, saracatinib (SCB) with human serum albumin (HSA), the major carrier protein in human blood circulation was investigated using fluorescence and absorption spectroscopy as well as computational methods. Analysis of the fluorescence quenching data along with absorption results confirmed the complex formation between SCB and HSA, based on the inverse correlation of the Stern-Volmer constant (K-SV) with temperature and hyperchromic effect in the absorption spectra. Moderate binding affinity between SCB and HSA was evident from the binding constant, K-a value (1.08-0.74 x 10(4) M-1), while the SCB-HSA complexation was anticipated to be stabilized by hydrophobic and van der Waals interactions along with hydrogen bonds, as revealed from the thermodynamic data (Delta S = + 29.40 J mol(-1) K-1 and Delta H = - 13.90 kJ mol(-1)). Addition of SCB to HSA significantly defended the thermal denaturation of the protein, though it perturbed the surrounding medium around Tyr and Trp residues. Site marker displacement results elucidated Sudlow's site I, positioned in subdomain IIA of HSA as the preferred binding site of SCB, which was well supported by molecular docking. Molecular dynamics simulation results suggested the stability of the SCB-HSA complex. Communicated by Ramaswamy H. Sarma