Evaluation of the interaction of novel tyrosine kinase inhibitor apatinib mesylate with bovine serum albumin using spectroscopies and theoretical calculation approaches.

Apatinib mesylate (APM), a novel tyrosine kinase inhibitor, has been applied in treating various cancers. In the present study, the binding mechanism of APM with bovine serum albumin (BSA) was studied by making use of various spectroscopic and theoretical calculation approaches to provide theoretical support for further studying its pharmacokinetics and metabolism. The results from fluorescence experiments showed that the quenching mechanism of BSA induced by APM was static quenching and the APM-BSA complex with the stoichiometry of 1:1 was formed during binding reaction. Moreover, the findings also showed that the binding process of APM to BSA was spontaneous and enthalpy-driven, and the mainly driving forces were hydrogen bonding, van der Waals as well as hydrophobic interactions. From the outcomes of the competitive experiments, it can be found that the binding site was primarily nestled in sub-domain IIIA of BSA (site II) which was in line with the results of molecular docking. An appreciable decline in α-helix content of BSA can be observed from the FT-IR data, meaning that the conformational change of BSA occurred after binding with APM, this phenomenon can be corroborated by the results of UV-vis, synchronous fluorescence and 3D fluorescence studies. Furthermore, the effect of some metal ions (e.g. K, Co, Ni, Fe) on the binding constant of APM to BSA was explored.Communicated by Ramaswamy H. Sarma.