In the present study, a novel p-hydroxycinnamic amide (E)-3-(4-hydroxyphenyl)-N-(4-(N-(5-meth oxypyrimidin-2-yl)-sulfamoyl)phenyl)acrylamide (HMSP) was synthesized and confirmed. In vitro cytotoxic assays indicated that HMSP was able to inhibit the proliferation of various cancer cell lines. The interaction between HMSP and human serum albumin (HSA) was examined by fluorescence, UV-Vis and circular dichroism (CD) spectra, in addition to molecular simulation. The fluorescence and UV-Vis spectra data indicated that the binding of HMSP with HSA was a static process. According to the fluorescence quenching calculation, the corresponding thermodynamic parameters, bimolecular quenching rate constant and apparent quenching constants were calculated. Van der Walls forces and hydrogen bonds were vital in the binding of HMSP on HSA. The distances between HSA and its derivatives were obtained. Furthermore, competitive experiments and molecular modeling results suggested that the binding of the compound on HSA mainly occurred in site I (sub-domain IIA). Changes in HSA conformation were observed from synchronous fluorescence and CD spectra, which were further investigated by molecular dynamic simulations.
Keywords: human serum albumin; interaction; p-hydroxycinnamic amides; synthesis; thermodynamics.