Molecular Recognition between Anticancer Drug, Regorafenib and Human Serum Albumin: Interaction Revisited
Salanee Kandandapani, Md. Zahirul Kabır, Hafsa Tayyab, Saharuddin Bin Mohamad, Saad Tayyab · Croatica Chemica Acta · 2022
The wet-lab techniques (fluorimetry and spectrophotometry), along with computational techniques (molecular docking and molecular dynamics (MD) simulation), were applied to re-examine the association of an anticancer drug, regorafenib (REG) with human serum albumin (HSA).The REG-induced protein fluorescence quenching was characterized as static quenching based on a decrement in the KSV (Stern-Volmer constant) with increasing temperature and hyperchromic effect in the absorption spectra.The REG-HSA complex (Ka = 0.63 -1.17 × 10 5 M -1 ) was stabilized by hydrophobic and van der Waals interactions in combination with hydrogen bonds, as revealed by thermodynamic data (ΔrS° = +17.17J mol -1 K -1 and ΔrH° = -23.00kJ mol -1 ), and further supported by molecular docking assessment.Microenvironmental fluctuations around HSA fluorophores and better protein stability against thermal stress were evident due to REG-HSA complexation.Accessibility of both Sudlow's Sites I and II but priority for Site I of the protein for REG was inferred by the competitive ligand displacement and molecular docking assessments.MD simulation results supported the stability of the complex.