Kandandapani, Salanee and Kabir, Md. Zahirul and Ridzwan, Nor Farrah Wahidah and Mohamad, Saharuddin B. and Tayyab, Saad (2022) Biomolecular interaction mechanism of an anticancer drug, pazopanib with human serum albumin: A multi-spectroscopic and computational approach. Journal of Biomolecular Structure and Dynamics, 40 (18). pp. 8312-8323. ISSN 0739-1102, DOI https://doi.org/10.1080/07391102.2021.1911850.
Full text not available from this repository.Abstract
Pazopanib (PZP) is a multi-targeting tyrosine kinase inhibitor and is currently approved by FDA for the treatment of soft tissue sarcoma and renal cancer. Molecular interaction mechanism of PZP with human serum albumin (HSA) was explored under simulated physiological conditions (pH = 7.4), using fluorescence and UV absorption spectroscopy along with computational methods. Based on the inverse correlation between the Stern-Volmer constant (Ksv) and temperature, it was concluded that PZP quenched the protein fluorescence through static quenching mechanism. This was also confirmed from the UV-vis absorption spectral results. Moderate binding affinity between PZP and HSA was evident from the Ka values (5.51 − 1.05 × 105 M−1) while PZP-HSA complex formation was driven by hydrophobic and van der Waals interactions as well as hydrogen bonds, as revealed by positive entropy change (ΔS = +98.37 J mol−1 K−1) and negative enthalpy change (ΔH = −60.31 kJ mol−1). Three-dimensional fluorescence spectral results disclosed microenvironmental perturbations around Trp and Tyr residues of the protein upon PZP binding. Interestingly, the addition of PZP to HSA significantly protected the protein against thermal stress. Competitive drug displacement results obtained with warfarin, phenylbutazone and diazepam elucidated Sudlow's Site I, positioned in subdomain IIA of HSA, as the preferred binding site of PZP which was well supported by molecular docking analysis, while molecular dynamics simulation results suggested the stability of the PZP-HSA complex. Communicated by Vsevolod Makeev. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya |
| Uncontrolled Keywords: | Fluorescence quenching; Human serum albumin; Ligand-protein interaction; Molecular dynamic simulations; Pazopanib |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 28 Jun 2025 02:58 |
| Last Modified: | 28 Jun 2025 02:58 |
| URI: | http://eprints.um.edu.my/id/eprint/40699 |
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