title: Characterization of interactions of simvastatin, pravastatin, fluvastatin, and pitavastatin with bovine serum albumin: multiple spectroscopic and molecular docking.
abstract: The binding interactions of simvastatin (SIM), pravastatin (PRA), fluvastatin (FLU), and pitavastatin (PIT) with bovine serum albumin (BSA) were investigated for determining the affinity of four statins with BSA through multiple spectroscopic and molecular docking methods. The experimental results showed that SIM, PRA, FLU, and PIT statins quenched the intrinsic fluorescence of BSA through a static quenching process and the stable stains-BSA complexes with the binding constants in the order of 104M-1at 298 K were formed through intermolecular nonbond interaction. The values of ΔH0, ΔS0and ΔG0in the binding process of SIM, PRA, FLU, and PIT with BSA were negative at the studied temperature range, suggesting that the binding process of four statins and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen-bonding interactions. Moreover, the binding of four statins with BSA was enthalpy-driven process due to |ΔH°|>|TΔS°| under the studied temperature range. From the results of site marker competitive experiments and molecular docking, subdomain IIIA (site II) was the primary binding site for SIM, PRA, FLU, and PIT on BSA. The results of UV-vis absorption, synchronous fluorescence, 3D fluorescence and FT-IR spectra proved that the slight change in the conformation of BSA, while the significant changes in the conformation of SIM, PRA, FLU, and PIT drug in statin-BSA complexes, indicating that the flexibility of statin molecules plays an important role in increasing the stability of statin-BSA complexes.
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou 310014 , China.|b State Key Laboratory Breeding Base of Green Chemistry Synthesis Technology , Zhejiang University of Technology , Hangzhou 310014 , China.
authors.forename: Jie-Hua
authors.initials: JH
authors.lastname: Shi
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou 310014 , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou 310014 , China.
authors.forename: Dong-Qi
authors.initials: DQ
authors.lastname: Pan
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou 310014 , China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Liu
authors.affiliation: a College of Pharmaceutical Science , Zhejiang University of Technology , Hangzhou 310014 , China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D000077340:Fluvastatin; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry*; D007700:Kinetics; D062105:Molecular Docking Simulation; D017035:Pravastatin / Q000737:chemistry*; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D019821:Simvastatin / Q000737:chemistry*; D012996:Solutions; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D011804:Quinolines; D012996:Solutions; D012710:Serum Albumin, Bovine; D000077340:Fluvastatin; D019821:Simvastatin; D017035:Pravastatin; C108475:pitavastatin
keywords: bovine serum albumin; fluvastatin; pitavastatin; pravastatin; simvastatin