Investigation of the separate and simultaneous bindings of warfarin and fenofibrate to bovine serum albumin

Abstract

Lipid-lowering drugs are often taken with anticoagulant drugs in hyperlipidemia patients. Fenofibrate (FNBT) and warfarin (WAR) are common clinical lipid-lowering drugs and anticoagulant drugs, respectively. A study of binding affinity, binding force, binding distance, and binding sites was performed to determine the interaction mechanism between drugs and carrier proteins (bovine serum albumin, BSA), as well as their effects on BSA conformation. Both FNBT and WAR can form complexes with BSA by van der Waals force and hydrogen bonds. WAR had a stronger fluorescence quenching effect on BSA, a stronger binding affinity, and greater effects on BSA conformation than FNBT. According to fluorescence spectroscopy and cyclic voltammetry, co-administration of drugs decreased one drug's binding constant to BSA and increased its binding distance. This suggested that each drug's binding to BSA was disturbed by each other, as well as each drug's binding ability to BSA was altered by the other. It was demonstrated that co-administration of drugs had greater effects on the secondary structure of BSA and microenvironment polarity surrounding amino acid residues, using multiple spectroscopy techniques, such as ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and synchronous fluorescence spectroscopy.