Abstract

Piperlongumine (PL) is a very promising natural agent with a high potential for cancer treatment. To overcome the poor water solubility of PL, there is a need to develop a novel water-soluble formulation in which PL is non-covalently bound to human serum albumin (HSA). PL binding to HSA was studied by various spectroscopic techniques under simulated physiological conditions. Spectroscopic evidence showed that the interaction of PL with HSA could form a PL–HSA complex. The binding constant (K a ) values increased with increasing temperature, and a similar dependence was observed for the number of binding sites (n) values. The number of PL molecules bound to HSA reached 8.1 when the temperature was raised to 308 K. Thermodynamic calculation results suggested that the binding reaction occurred spontaneously but was an entropy-driven process, and hydrophobic forces played a major role in stabilizing the complex. Furthermore, PL binding induced conformational and microenvironmental changes in HSA. Displacement studies indicated that PL and warfarin had separate binding regions in site I. Therefore, it would be possible to develop a novel water-soluble formulation involving PL and HSA. This study may provide some valuable information in terms of improving the poor water solubility of PL.