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The development of new drugs especially novel anti-cancer drugs has become a hot-spot issue that catches scholars’ attention in every field. Here a IAP antagonist analogue (IAPA) was synthesized and characterized by NMR and HRMS spectra. Its interaction with proteins, including bovine serum albumin (BSA) and human serum albumin (HSA), were investigated by spectral methods and molecular simulation. Fluorescence quenching, together with UV absorption spectrum and time-resolved fluorescence spectrums indicated a static process in BSA/HSA-IAPA system. Thermodynamic parameters including ΔH and ΔS calculated by Vant't Hoff equation were all positive, showing that hydrophobic force was the major force in the interaction of compound IAPA and BSA/HSA. Site marker competitive displacement experiments proved that IAPA bound to site I at BSA/HSA. Synchronous fluorescence spectrum and three-dimensional fluorescence spectrum were also used to investigate the conformational changes of BSA/HSA after binding with compound IAPA. The above results were further verified by molecular docking.

Here we synthesized four 3-fluorooxindole derivatives and investigated their affinity interactions with serum albumin by using multi-spectral, electrochemical, and molecular docking. Fluorescence spectroscopy results revealed the affinity of 3-fluorooxindole derivatives and serum albumin. UV spectroscopy showed the type of quenching for both were static quenching, which was proved by temperature dependence experiments and time-resolved fluorescence. Electrochemical experiment results suggested the binding constant of 3-fluorooxindole derivatives and serum albumin was 103–104 by the order of magnitude. Synchronous fluorescence spectroscopy and infrared spectroscopy demonstrated the effect on the secondary structure of serum albumin in the presence of 3-fluorooxindole units. Furthermore, molecular docking and site competition experiments result determined that 3-fluorooxindole derivatives bind to site I of serum albumin. Finally, the interactions between 3-fluorooxindole derivatives and serum albumin were investigated by various methods and summarized the effects of substituents in 3-fluorooxindole derivatives on serum albumin interactions. These results provide a reference for the design of subsequent synthesis of 3-fluorooxindole derivatives and theoretical support for the development of related fluorine-containing drugs.