Molecular Recognition between Anticancer Drug, Regorafenib and Human Serum Albumin: Interaction Revisited

Croatica Chemica Acta

article

Salanee Kandandapani¹  Zahirul Kabir¹  Hafsa Tayyab²  Saharuddin B. Mohamad²  Saad Tayyab³ 

[1] Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya;Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya;Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University

关键词: human serum albumin;    regorafenib;    fluorescence quenching;    ligand-protein interaction;    molecular dynamics simulations;   

DOI  :  10.5562/cca3922

学科分类：化学（综合）

来源: Croatica Chemica Acta

【 摘 要 】

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 × 105 M–1) was stabilized by hydrophobic and van der Waals interactions in combination with hydrogen bonds, as revealed by thermodynamic data (ΔrS° = +17.17 J mol–1 K–1 and ΔrH° = –23.00 kJ 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.

【 授权许可】

CC BY