羟基肉桂酸衍生物的合成及其与人血清白蛋白的相互作用

Preparation of Hydroxy-cinnamic Acid Derivatives and Their Interaction with Human Serum Albumin

摘要:

以咖啡酸、间羟基肉桂酸为母体，分别与止血芳酸反应，设计合成两种羟基肉桂酸衍生物I、II，并用MS、IR、1H-NMR、13C-NMR进行结构表征。采用荧光光谱法、同步荧光光谱法、紫外可见光谱法结合分子对接技术研究其在体外生理条件下与HSA之间的相互作用机制。光谱实验结果表明，衍生物I和II都可以使HSA的内源荧光发生静态猝灭，相互作用力主要是氢键和范德华力，且对HSA的构象产生一定的影响。分子对接结果表明衍生物I、II与HSA中的结合位于亚结构域IIA（即site I）中，作用力主要是氢键和范德华力，同时还存在着疏水作用，且衍生物距色氨酸残基(Trp214)很近，很好地解释了衍生物有效猝灭HSA内源荧光的实验现象。分子对接与实验获得了一致性的结果，二者相互作证，提高了实验结果推断的准确度。

Abstract:

Two hydroxy-cinnamic acid derivatives (I and II) were synthetised by the reaction of Caffeic acid, m-hydroxybenzoic acid with p-aminomethylbenzoic acid (AMBA), respectively. The chemical structures were confirmed by MS, IR, 1H-NMR and 13C-NMR. The interactions between compounds and HSA were investigated under imitated physiological condition by fluorescence spectroscopy, UV-visible absorption spectroscopy and Molecular docking. The experimental results indicated that the quenching mechanism of HSA by the derivatives was static quenching mechanism at different temperatures. The derivatives-HSA interactions were mainly driven by hydrogen bonds and van der Waals’ forces. Meanwhile, derivatives I and II affected the conformation of HSA. The molecular docking represented that derivatives I and II existed in subdomain IIA (site I) of HSA. Furthermore, derivatives were closed to tryptophan residues (Trp214). The results revealed that the intrinsic fluorescence of HSA could be successfully decreased by derivatives interactions. The experimental results were in agreement with molecular docking.