Comparative Interactions of Dihydroquinazolin Derivatives with Human Serum Albumin Observed via Multiple Spectroscopy

The interactions of dihydroquinazolines with human serum albumin (HSA) were studied in pH 7.4 aqueous solution via fluorescence, circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopic techniques. In this work, 6-chloro-1-(3,3-dimethyl-butanoyl)-2(un)substitutedphenyl-2,3-dihydroquinazolin-4(1H)-one (PDQL) derivatives were designed and synthesized to study the impact of five similar substituents (methyl, methoxy, cyano, trifluoromethyl and isopropyl) on the interactions between PDQL and HSA using a comparative methodology. The results revealed that PDQL quenched the intrinsic fluorescence of HSA through a static quenching process. Displacement experiments with site-specific markers revealed that PDQL binds to HSA at site II (subdomain IIIA) and that there may be only one binding site for PDQL on HSA. The thermodynamic parameters indicated that hydrophobic interactions mainly drove the interactions between PDQL and HSA. The substitution using five similar groups in the benzene ring could increase the interactions between PDQL and HSA to some extent through the van der Waals force or hydrogen bond effects in the proper temperature range. Isopropyl substitution could particularly enhance the binding affinity, as observed via comparative studies