Xanthoxylin (XAN) is a phenolic compound with well-known bioactivities, including antitumor action, that is exclusively found in the Zanthoxylum genus, commonly known as Szechuan pepper. The interplay between pharmacologically active agents and serum albumin is essential and relevant to pharmacokinetics and pharmacodynamics. This study examines the interaction between XAN and human serum albumin (HSA) using spectroscopic techniques and molecular docking, thereby expanding the scope of previous research, which has primarily focused on bovine serum albumin (BSA). The slight differences in the amino acid sequences of HSA and BSA may influence the binding characteristics of XAN. Absorption and fluorescence spectroscopy affirmed the formation of a complex between XAN and HSA. XAN quenched the intrinsic fluorescence of HSA via static mode, and the binding constant was in the order of 104 M-1, indicating moderate affinity. Thermochemical analyses revealed that the interaction is spontaneous, driven by hydrogen bonds and van der Waals forces. Forster resonance energy transfer demonstrated efficient energy transfer from HSA to XAN, while 3D fluorescence and circular dichroism spectroscopy indicated conformational changes in HSA upon binding to XAN. The thermal denaturation profile suggested that XAN destabilises HSA. Competitive displacement studies and molecular docking projected Site I of HSA as the favoured binding site for XAN . The acting forces computed by docking align with the forces deduced by thermodynamics analysis. The presence of Cu and Zn metal ions influences the binding affinity of XAN for HSA. Additionally, thebilirubin (BR) displacement studies indicate that XAN exhibits minimal displacement of BR.
Afaq et al. (Wed,) studied this question.