Exploring the binding mechanism of dihydropyrimidinones to human serum albumin: spectroscopic and molecular modeling techniques.

The binding mechanism of molecular interaction between 5-(ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (a dihydropyrimidinones derivative, EMPD) and human serum albumin (HSA) was studied using spectroscopic methods and modeling technique. The quenching mechanism was investigated in terms of the binding constants and the basic thermodynamic parameters. The results of spectroscopic measurements suggested that EMPD have a strong ability to quench the intrinsic fluorescence of HSA through static quenching procedure. The drug-protein complex was stabilized by hydrophobic forces and hydrogen bonding as indicated from the thermodynamic parameters and synchronous fluorescence spectra, which was consistent with the results of molecular docking and accessible surface area calculation. Competitive experiments indicated that a displacement of warfarin by EMPD, which revealed that the binding site of EMPD to HSA was located at the subdomains IIA. The distance between the donor and the acceptor was 4.85nm as estimated according to Förster's theory of non-radiation energy transfer. The effect of metal ions on the binding constants was also investigated. The results indicated that the binding constants between EMPD and HSA increased in the presence of common metal ions.