Liu Yu, Li Qian-Yu, Wang Yu-Ping, Liu Yi-Ming, Liu Bin, Liu Mei-Mei, Liu Bing-Mi
College of Pharmacy, Liaoning University, Shenyang, People's Republic of China.
Key Laboratory of New Drug Research and Development of Liaoning Province, Shenyang, People's Republic of China.
Luminescence. 2018 Mar;33(2):305-311. doi: 10.1002/bio.3414. Epub 2017 Oct 18.
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 ) 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.
胡椒碱（PL）是一种非常有前景的天然药物，在癌症治疗方面具有很高的潜力。为了克服PL水溶性差的问题，需要开发一种新型水溶性制剂，其中PL与人血清白蛋白（HSA）非共价结合。在模拟生理条件下，通过各种光谱技术研究了PL与HSA的结合。光谱证据表明，PL与HSA的相互作用可形成PL-HSA复合物。结合常数（K）值随温度升高而增加，结合位点数（n）值也呈现类似的依赖性。当温度升至308 K时，结合到HSA上的PL分子数达到8.1。热力学计算结果表明，结合反应是自发发生的，但为熵驱动过程，疏水作用力在稳定复合物中起主要作用。此外，PL结合诱导了HSA的构象和微环境变化。置换研究表明，PL和华法林在位点I有各自独立的结合区域。因此，有可能开发一种涉及PL和HSA的新型水溶性制剂。本研究可能为改善PL水溶性差的问题提供一些有价值的信息。
