Interaction Between Toddalolatone and Human Serum Albumin

A combination of fluorescence, UV–Vis absorption, circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopic and molecular modeling approaches was employed to investigate the interaction between toddalolactone (TDT) and human serum albumin (HSA) at physiological buffer conditions (pH 7.4). Fluorescence titration suggests that the mechanism of the fluorescence quenching of HSA is static, resulting from the formation of a TDT–HSA complex. Binding parameters calculated from the modified Stern–Volmer equation show that TDT binds to HSA with high affinity. Negative enthalpy change and positive entropy change values suggest that the binding process is primarily driven by hydrophobic interactions and hydrogen bonds. The binding of TDT to HSA results in an increase in the surface hydrophobicity of HSA. The binding distance between the Trp-214 residue (donor) and TDT (acceptor) was determined to be 4.18 nm based on the Förster theory of non-radioactive energy transfer. Displacement studies of site markers reveal that the binding site of TDT to HSA is located in the subdomain IIA (Sudlow’s site I). Furthermore, the molecular docking results corroborate and illustrate the specific binding mode and binding site. Analysis of UV–Vis absorption, CD and FT-IR spectra demonstrated that TDT induced a small alteration of the protein’s conformation.