Study on the interaction of two quinazolin 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 quinazolin derivatives, S1 and S2 , 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's fluorescence could be statically quenched by S1 and S2 through the formation of the HSA-drug complex. Furthermore, the details of the binding site number, binding constant, as well as 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 S1 or S2 . Synchronous fluorescence and ultraviolet (UV) absorption spectra suggested that S1 and S2 had little effect on the polarity of the microenvironment and conformation of HSA. Energy transfer from HSA to S1 or S2 was most probably occurred. The docking study revealed that S1 and S2 were able to bind to the hydrophobic cavity which was located in HSA's subdomain IIA and form varying numbers of hydrogen bonds with amino acid residues nearby. Due to the subtle difference in the chemical structure, the binding of S1 and S2 to HSA was slightly different.