Cardiovascular Drugs And Human Serum Albumin Interaction

Objective The interaction between ozagrel, sodium ferulate, aceglutamide, buflomedil, vinpocetine, scutellarin and human serum albumin (HSA) were investigated under simulative physiological condition and the binding mode of six drugs with HSA was explored from different perspectives.Methods The changes of the UV-vis absorbance and the electrochemical property before and after the interaction between ozagrel, sodium ferulate, aceglutamide, buflomedil, vinpocetine, scutellarin and human serum albumin(HSA) was studied by the Ultraviolet difference spectra, Cyclic voltammetry and Differential pulse voltammetry. The parameters of the interaction between drugs and HSA was obtained by the fluorescence quenching titration, including the binding constant, quenching rate constant, the number of binding sites, binding distance, the interaction force, and the influence of metal ions such as K⁺,Fe³⁺,Cu²⁺,Zn²⁺,Mg²⁺ on the interaction; The effects of drugs on the conformation of HSA were studied using synchronous fluorescence spectroscopy; furthermore, the variations of protein secondary structure due to the drugs were quantitatively analyzed by the Fourier transformation infrared spectra (FT-IR) combined with curve-fitting technique.Results The intrinsic fluorescence of HSA was quenched by six drugs respectively. The quenching mechanism of aceglutamide on HSA was dynamic quenching. The 1:1 complexes were formed between ozagrel, sodium ferulate, buflomedil, vinpocetine and HSA, meanwhile, their binding constants were 2.34×10⁵, 8.22×10⁴, 1.54×10³ and 7.83×10² L·mol^-1 with binding distances of 1.75, 1.01, 2.59 and 2.64nm respectively. With two kinds of binding sites on HSA, the binding constants of scutellarin-HSA were 6.92×10³ and 7.93×10⁶ L·mol^-1 respectively. Six drugs all caused changes on peak intensity, peak shape, AmideⅠandⅡbands of HSA peptide chain.Conclusion Six drugs all have an interaction with HSA, which changed the conformation of HSA. As to ozagrel, sodium ferulate, aceglutamide and scutellarin, hydrophobic interaction was the predominant binding force, while the interaction between vinpocetine, buflomedil and HSA was mainly driven by hydrogen bond and van der Waals. The interaction between six drugs and HSA was influenced differently by ions. After the interaction with drugs, the secondary structure of HSA was changed fromα-helix toβ-sheet andβ-turn, which induced the protein structure unfold to a more loose conformation and the physiological and biochemical function of protein was changed consequently.