新型药物2-甲基-2,4-二乙氧羰基-6-三氟甲氧基-1,2-二氢喹啉的合成及其与HSA的相互作用

Synthesis of 2-methyl-2,4-diethoxycarbonyl-6-trifluoromethoxy-1,2-dihydroquinoline and the study of its interaction with HSA

合成了一种新化合物2-甲基-2,4-二乙氧羰基-6-三氟甲氧基-1,2-二氢喹啉(M DTDQ),采用共振光散射法(RLS)、荧光光谱法、紫外光谱法以及电化学阻抗法(EIS)研究了MDTDQ与人血清白蛋白(HSA)的作用机理。电化学阻抗及共振光散射光谱分析表明HSA与MDTDQ发生结合形成了复合物;MDTDQ对HSA有荧光猝灭作用,由Stern-Volmer方程以及紫外吸收光谱判断其猝灭过程主要为静态猝灭;通过双对数方程计算出298 K,304 K,310 K时两者的结合常数及其相应的结合位点数;根据热力学参数方程计算出△H、△S和△G的值分别为-64.28 k J/mol,-131.70 J·mol-1·K-1,-24.95k J/mol,推断两者之间的作用力类型主要是氢键和范德华力;由Frster非辐射能量转移理论得到MDTDQ与HSA的结合距离为2.85 nm;同步荧光光谱数据表明MDTDQ引起了HSA构象的变化。采用分子模拟对接分析了MDTDQ与HSA的结合,所得结论与实验研究结果一致。

A new compound,2-methyl-2,4-diethoxycarbonyl-6-trifluoromethoxy-1,2-dihydroquinoline（ MDTDQ） was synthesized. The interaction between HSA and MDTDQ was explored by using five measurements including resonance light scattering spectroscopy（ RLS）,fluorescence,UV-vis absorbance spectroscopy and electrochemical impedance spectroscopy（ EIS）. EIS and RLS showed that MDTDQ might bind to HSA via the formation a MDTDQ-HSA complex. The fluorescence of HSA was quenched by MDTDQ and the mechanism was proved to be static quenching procedure according to Stern-Volmer equation and UV-vis absorbance spectroscopy. Binding constants and binding site numbers at 298 K,304 K,and 310 K were calculated according to double logarithm regression curve,respectively. The thermodynamic parameters △H,△S and △G were obtained to be- 64. 28 k J·mol^-1,- 131. 7 J·mol·K^- 1,and- 24. 95 k J·mol^-1 based on the thermodynamic equations,which indicated that the action force was mainly hydrogen bonds and van der Waals force. The distance between MDTDQ and HAS was estimated to be 2. 85 nm（ 298 K） based on the Fster non-radioactive energy transfer theory. Effect of MDTDQ on the conformation of HAS has been investigated by means of synchronous fluorescence spectroscopy,which indicated the addition of MDTDQ changed the conformation of HAS. In addition,molecular docking was used to research the combination between MDTDQ and HAS,and the conclusions are in agreement with the experimental results.