以间甲氧基肉桂酸、对位取代的苯甲醛为原料, 设计合成了2种未见报道的肉桂酸肟酯类衍生物, 并用MS、IR、1H NMR、13C NMR进行结构表征。采用分子对接技术和荧光光谱法、紫外-可见光谱法、位点竞争法研究了2种衍生物分别和人血清白蛋白(HSA)相结合的机理。通过Stern-Volmer方程等处理荧光猝灭相关数据得到了衍生物与HSA相互作用的结合常数和热力学参数。结合紫外-可见光谱对两种衍生物与HSA的相互作用进行了进一步的分析, 结果表明在体外生理条件下, 衍生物都可以与HSA结合, 对HSA内源荧光产生静态猝灭并对其构象产生影响, 其主要的结合力为氢键和范德华力。位点竞争实验表明衍生物与HSA相互作用都发生在Sudlow site 1(亚域Ⅱ A)处。以上实验结果均验证了分子模拟对实验的预测。

Two novel cinnamic acid oxime ester derivatives were designed and synthesized with o-methoxy cinnamic acid and p-substituted benzaldehyde. Their structures were characterized by mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance. The interaction mechanism of derivatives and human serum albumin (HSA) were explored by molecular docking, fluorescence spectroscopy, UV-visible absorption spectroscopy and site marker competitive experiments．The binding constants and corresponding thermodynamic parameters of the derivative-HSA systems were calculated by Stern-Volmer equation. Combined with UV-Vis absorption spectra, the results indicate that the derivatives can get complexes with HSA respectively and strongly quench the intrinsic fluorescence of HSA, and hydrogen bonds and van der Waals forces are main acting forces. Site marker competitive experiments indicate that the binding of the derivatives to HSA primarily take place in sub-domain ⅡA. The above results verify the prediction of molecular simulation experiment.