杜鹃素新结构衍生物与人血清白蛋白相互作用的光谱及分子对接  

Spectroscopic studies and molecular docking on the interaction of a new structure derivative of farrerol with human serum albumin

作　　者：李洁[1] 董红周[1] 卫莺 刘恩荔[1] 

机构地区：[1]山西医科大学药学院,太原030001

出　　处：《分析试验室》2017年第6期637-642,共6页Chinese Journal of Analysis Laboratory

基　　金：国家自然科学基金(81172938);山西省青年科技基金(201601D021158);山西省研究生优秀创新项目;山西医科大学科技创新基金(01201303)资助

摘　　要：采用光谱法及分子对接法考察了该化合物与人血清白蛋白(HSA)的相互作用。荧光光谱分析表明,DJS-NO_2对HSA的荧光有明显的猝灭作用,其机制属于静态荧光猝灭;温度为25℃和37℃时,猝灭常数分别为6.691×10^(13)mol/(L·s)和3.433×10^(13)mol/(L·s);结合常数分别为4.914×10~5mol/L和4.610×10~5mol/L,具有一个结合位点。热力学分析表明,该化合物与HSA之间的结合以疏水作用力为主;三维荧光光谱分析表明DJS-NO_2导致HSA氨基酸残基微环境和二级构象发生变化。圆二色谱分析显示二者的结合使得HSA的α-螺旋含量减少,提示HSA构象发生变化。分子模拟结果显示DJS-NO_2主要与HSA的位点I结合,且该化合物通过氢键与ALA118结合最紧密。The binding ability of drugs and human serum albumin has became an important index to design and evaluate the new drugs. A new structure derivative of farrerol, 5,7-dihydroxy- 6,8- dimethyl- 2 - （2-nitrophenyl）chroman -g-ketone （DJS-NO2）, exhibited good in vitro anti- proliferation effects against the rat vscular smooth muscle cells （VSMCs）. The interactions of this compound with human serum album （HSA） were investigated using spectroscopic studies （i. e., fluorescence, three-dimensional fluorescence and circular dichroism spectroscopies ）and molecular docking. The fluorescence results showed that DJS-NO2 strongly quenched the fluorescence of HSA, and the interaction was a static quenching process. At 25℃ and 37℃, the quenching constants of DJS- NO2 with HSA was 6. 691 × 10^13mol/（ L · s） and 3. 433 ×10^13mol/（ L · s） respectively. The binding constants were 4. 9147 × 10^5mol/L and 4. 610 × 10^5mol/L, respectively. And the number of binding site was 1. Hydrophobic interactions played an important role in the HSA-DJS-NO2 interactions, as indicated by the thermodynamic parameters. The 3 D florescence revealed that the microenvironment of amino acid residues and the conformation of HSA were changed during the binding interaction. Moreover, the CD results also explained the conformational changed in the HSA on binding with DJS- NO2. The α-helical structure was slightly decreasing. The molecular docking results showed that DJS-NO2 can bind with HSA in site I. It also showed that the predicted binding modes of DJS in HSA protein appeared to be adopted an orientation with interaction of ALAll8 by hydrogen bonds. The study is of great significance to drug screening and understanding of the mechanism of compounds.

关 键 词：5 7-二羟基-2-(6-硝基苯基)-6 8-二甲基苯并二氢吡喃-4-酮 人血清白蛋白 相互作用 光谱法 分子对接 

分 类 号：O641.3[理学—物理化学] O657.3[理学—化学]