Study on the interaction of two quinazoline derivatives as novel PI3K/mTOR dual inhibitors and anticancer agents to human serum albumin utilizing spectroscopy and docking.

Interactions of human serum albumin (HSA) with two structurally similar quinazoline derivatives, S and S , which are potential anticancer drugs acting on PI3K/mTOR targets, were investigated in vitro utilizing multiple spectroscopy as well as molecular docking. The fluorescence quenching study demonstrated that HSA fluorescence could be statically quenched by S and S through the formation of an HSA-drug complex. Furthermore, the details of the binding site number, binding constant, as well as the thermodynamic parameters, were estimated at 298, 303, and 310 K. The results revealed that hydrogen bond interactions, as well as van der Waals forces, were the predominant factors responsible for binding HSA to S or S . Synchronous fluorescence and ultraviolet (UV) absorption spectra suggested that S and S had little effect on the polarity of the microenvironment and conformation of HSA. Energy transfer from HSA to S or S most probably occurred. The docking study revealed that S and S were able to bind to the hydrophobic cavity that was located in the HSA subdomain IIA and formed varying numbers of hydrogen bonds with amino acid residues nearby. Due to the subtle difference in the chemical structure, the binding of S and S to HSA was slightly different.