光谱法结合分子模拟技术研究磺胺甲恶唑与左氧氟沙星的协同作用

在模拟人体生理酸度(pH=7.4)条件下,运用荧光光谱、紫外光谱和分子模拟技术,研究了磺胺甲恶唑(SMZ)和左氧氟沙星(LVFX)的协同作用.实验结果表明,SMZ、LVFX主要通过氢键和疏水作用与人血清白蛋白(HSA)发生相互作用形成复合物,导致HSA的内源荧光发生静态猝灭.SMZ、LVFX在HSA上有相同的结合位点,即Site I位.在HSA-SMZ(或HSA-LVFX)体系中分别加入LVFX(或SMZ),其结合常数均明显减小,表明LVFX(或SMZ)的存在削弱了HSA-SMZ(或HSA-LVFX)体系的结合能力,使得LVFX(或SMZ)更多被释放,血液中游离的LVFX(或SMZ)浓度增大,SMZ与LVFX共存能够协同增强药效.

Study on the Synergistic Effects between Sulfamethoxazole and Levofloxacin by Spectroscopic and Molecular Modeling Techniques

The synergistic effects between sulfamethoxazole (SMZ) and levofloxacin (LVFX) on human serum albumin(HSA) was investigated in simulative physiological buffer(pH =7.4) by fluorescence,UV-Vis absorption and molecular modeling techniques.The results revealed that the fluorescence quenching of HSA by SMZ or LVFX was considered as a static quenching process.The interaction between SMZ or LVFX and HSA was mainly driven by hydrogen bonds and hydrophobic force,and the binding of SMZ or LVFX to HSA mainly located in the same binding site,namely Site I.With the addition of LVFX(SMZ),the binding constant of HSA SMZ(HSA-LVFX) system decreased.It was demonstrated that the existence of LVFX (SMZ) led to the decrease of the binding stability between SMZ(LVFX) and HSA.As a result,the free concentration of SMZ(LVFX) in blood increased,which indicated that there was a synergistic effect when SMZ and LVFX coexisted.