Khaibrakhmanova Diliara, Nikiforova Alena, Sedov Igor
Chemical Institute, Kremlevskaya 18, Kazan Federal University, 420008 Kazan, Russia.
Pharmaceuticals (Basel). 2020 Feb 20;13(2):30. doi: 10.3390/ph13020030.
Experimental data on the affinity of various substances to albumin are essential for the development of empirical models to predict plasma binding of drug candidates. Binding of 24 substituted benzoic acid anions to bovine serum albumin was studied using spectrofluorimetric titration. The equilibrium constants of binding at 298 K were determined according to 1:1 complex formation model. The relationships between the ligand structure and albumin affinity are analyzed. The binding constant values for m- and p-monosubstituted acids show a good correlation with the Hammett constants of substituents. Two- and three-parameter quantitative structure-activity relationship (QSAR) models with theoretical molecular descriptors are able to satisfactorily describe the obtained values for the whole set of acids. It is shown that the electron-density distribution in the aromatic ring exerts crucial influence on the albumin affinity.
各种物质与白蛋白亲和力的实验数据对于开发预测候选药物血浆结合的经验模型至关重要。采用荧光光谱滴定法研究了24种取代苯甲酸阴离子与牛血清白蛋白的结合。根据1:1络合物形成模型测定了298K时的结合平衡常数。分析了配体结构与白蛋白亲和力之间的关系。间位和对位单取代酸的结合常数与取代基的哈米特常数具有良好的相关性。具有理论分子描述符的二参数和三参数定量构效关系（QSAR）模型能够令人满意地描述整个酸系列的所得值。结果表明，芳环中的电子密度分布对白蛋白亲和力有至关重要的影响。
