Multi-Spectroscopic, thermodynamic and molecular dynamic simulation studies for investigation of interaction of dapagliflozin with bovine serum albumin

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 264; p. 120298
• Main Authors: Abdelaziz, Mohamed A., Shaldam, Moataz, El-Domany, Ramadan A., Belal, Fathalla
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-01-2022
• Subjects: Binding thermodynamic parameters; Bovine serum albumin; Dapagliflozin; Docking; Fluorescence; Quenching; Spectroscopy; Bovine serum albumin; Spectroscopy; Dapagliflozin; Fluorescence; Docking; Binding thermodynamic parameters; Quenching
• ISSN: 1386-1425
• DOI: 10.1016/j.saa.2021.120298

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•The binding interaction between dapagliflozin andbovine serum albumin (BSA) was studied applying multi-spectroscopic techniques for the first time.•Dapagliflozin binds BSA at Site I as reveled by site marker competitive studies.•The thermodynamic studies showedslight conformational changes in BSA by binding with dapagliflozin.•The stability of dapagliflozin-BSA complex was predicted by molecular docking and supported by MD simulations.
Dapagliflozin (DAPA) is a selective sodium-glucose cotransporter-2 inhibitor that reduces renal glucose reabsorption. The drug has recently become a crucial milestone in the management of diabetes and heart failure. In this study, the interaction of DAPA with bovine serum albumin (BSA) was investigated for the first time using various fluorescence spectroscopic techniques, UV-absorption spectroscopy, molecular docking, and molecular dynamic (MD) simulation. The fluorescence spectroscopic titration study performed at different temperatures showed that DAPA quenched the fluorescence of BSA through a combination of dynamic and static mechanisms, which was confirmed by UV absorption, fluorescence-resonance energy transfer measurements, and MD simulation. The binding thermodynamic parameters demonstrated that the binding stoichiometry between BSA and DAPA was 1:1. Competitive binding experiments using site-specific markers as well as molecular docking studies showed that DAPA binds to site I on BSA. The positive values of enthalpy change (ΔH) and entropy change (ΔS) revealed that hydrophobic forces played a predominant role in the binding of DAPA to BSA, whereas the negative value of Gibbs free energy change (ΔG) indicated the spontaneity of the interaction. Moreover, the synchronous fluorescence spectroscopy has shown that DAPA binding to the protein molecule occurs in the vicinity of the tryptophan residue. These findings were confirmed by the molecular docking and MD simulation studies.