Study of binding interaction of rivaroxaban with bovine serum albumin using multi-spectroscopic and molecular docking approach

Chemistry Central Journal

Seema Zargar¹  Haitham AlRabiah²  Ahmed H. Bakheit²  Tanveer A. Wani²  Mohd Abul Kalam³ 

[1] Department of Biochemistry, College of Science, King Saud University;Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University;Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University;

关键词: Bovine serum albumin;    Rivaroxaban;    Human serum albumin;    Fluorescence;    Quenching;   

DOI  :  10.1186/s13065-017-0366-1

来源: DOAJ

【 摘 要 】

Abstract Background Rivaroxaban is a direct inhibitor of coagulation factor Xa and is used for venous thromboembolic disorders. The rivaroxaban interaction with BSA was studied to understand its PK and PD (pharmacokinetics and pharmacokinetics) properties. Multi-spectroscopic studies were used to study the interaction which included UV spectrophotometric, spectrofluorometric and three dimensional spectrofluorometric studies. Further elucidation of data was done by molecular simulation studies to evaluate the interaction behavior between BSA and rivaroxaban. Results Rivaroxaban quenched the basic fluorescence of BSA molecule by the process of static quenching since rivaroxaban and BSA form a complex that results in shift of the absorption spectra of BSA molecule. A decline in the values of binding constants was detected with the increase of temperatures (298–308 K) and the binding constants were in range from 1.32 × 105 to 4.3 × 103 L mol−1 indicating the instability of the BSA and rivaroxaban complex at higher temperatures. The data of number of binding sites showed uniformity. The site marker experiments indicated site I (sub-domain IIA) as the principal site for rivaroxaban binding. The thermodynamic study experiments were carried at the temperatures of 298/303/308 K. The ∆G0, ∆H0 and ∆S0 at these temperatures ranged between − 24.67 and − 21.27 kJ mol−1 and the values for ∆H0 and ∆S0 were found to be − 126 kJ mol−1 and ∆S − 340 J mol−1 K−1 The negative value of ∆G0 indicating spontaneous binding between the two molecules. The negative values in ∆H0 and ∆S0 indicated van der Waals interaction and hydrogen bonding were involved during the interaction between rivaroxaban and BSA. Conclusions The results of molecular docking were consistent with the results obtained from spectroscopic studies in establishing the principal binding site and type of bonds between rivaroxaban and BSA.

【 授权许可】

Unknown