Janicka Małgorzata, Pachuta-Stec Anna
Department of Physical Chemistry, Faculty of Chemistry, Maria Curie-Skłodowska University, Lublin, Poland.
J Sep Sci. 2014 Jun;37(12):1419-28. doi: 10.1002/jssc.201400192. Epub 2014 May 2.
The properties of 21 1,2,4-triazoles, relevant to their pharmacokinetics, were investigated using experimental methods and in silico calculations. The lipophilicities of the compounds were determined experimentally using reversed-phase chromatography and liquid chromatography with micellar mobile phases, or they were calculated in silico from their molecular structures. In the reversed-phase technique, an octadecylsilyl, immobilized artificial membrane and immobilized cholesterol were used as the stationary phases. Biological descriptors of compounds, i.e. log BB, log KHSA, Caco-2, and fu,brain, were determined in silico by using ACD/Percepta software. Principal component analysis was used to indicate similarities between chromatographic, partitioning, and biological variables. Highly significant relationships were determined to exist between the chromatographic parameters and the biological descriptors, especially for log BB and log KHSA. The chromatographic parameters measured on the cholesterol column were recommended for use in predicting the lipophilic and biological properties of the 1,2,4-triazoles that were tested.
采用实验方法和计算机模拟计算，研究了21种1,2,4 - 三唑类化合物与其药代动力学相关的性质。通过反相色谱法和胶束流动相液相色谱法实验测定化合物的亲脂性，或者根据其分子结构进行计算机模拟计算。在反相技术中，使用十八烷基硅烷、固定化人工膜和固定化胆固醇作为固定相。利用ACD/Percepta软件通过计算机模拟确定化合物的生物学描述符，即log BB、log KHSA、Caco - 2和fu,brain。主成分分析用于表明色谱、分配和生物学变量之间的相似性。已确定色谱参数与生物学描述符之间存在高度显著的关系，尤其是对于log BB和log KHSA。建议使用在胆固醇柱上测量的色谱参数来预测所测试的1,2,4 - 三唑类化合物的亲脂性和生物学性质。
