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Croatica Chemica Acta, Vol. 95 No. 2, 2022.

Original scientific paper

https://doi.org/10.5562/cca3922

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

Salanee Kandandapani orcid id orcid.org/0000-0003-2134-1464 ; Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
Md. Zahirul Kabir orcid id orcid.org/0000-0003-0957-5073 ; Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
Hafsa Tayyab orcid id orcid.org/0000-0002-3057-9709 ; Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
Saharuddin B. Mohamad ; Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
Saad Tayyab orcid id orcid.org/0000-0003-1826-3098 ; Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia

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Abstract

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.

Keywords

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

Hrčak ID:

293919

URI

https://hrcak.srce.hr/293919

Publication date:

3.2.2023.

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