Interaction of Ketoconazole with Bovine Serum Albumin : ELectrochemical, Spectroscopic and Molecular Modeling Studies

Abstract

The interaction of ketoconazole (KTZ) with bovine serum albumin (BSA) has been investigated by cyclicvoltammetry, differential pulse voltammetry, UV-Vis absorption and fluorescence spectroscopy, viscositymeasurements as well as molecular modeling methods. The measurements were performed in 0.1 mol L-1phosphat buffer solution at pH = 7.4. Shifts in the peak potentials in cyclic Voltammetry, spectral changes in UVabsorption and fluorescence titration, an increase in viscosity of BSA and the molecular modeling methodsstrongly support the electrostatic interaction between KTZ and BSA. The thermodynamic parameters ΔH, ΔG andΔS at different temperatures were calculated, showing that the electrostatic interactions and hydrophobicinteraction are the main forces for the binding of KTZ to BSA. The binding constant (Kb) determined by UVabsorption and fluorescence measurements are very close to the value determined by cyclic Voltammetryassuming that the binding equilibrium is static. Moreover, from molecular modeling method, a docked structurewith minimum energy was obtained in which KTZ was located in minor grooves of BSA.