Department of Physical Chemistry, Faculty of Chemistry, Institute of Chemical Science, Maria Curie-Skłodowska University, Maria Curie-Skłodowska Sq. 3, 20-031 Lublin, Poland.
Doctoral School of Quantitative and Natural Sciences, Maria Curie-Skłodowska University, Maria Curie-Skłodowska Sq. 3, 20-031 Lublin, Poland.
Int J Mol Sci. 2021 Apr 20;22(8):4257. doi: 10.3390/ijms22084257.
The Quantitative Structure-Activity Relationship (QSAR) methodology was used to predict biological properties, i.e., the blood-brain distribution (log ), fraction unbounded in the brain (), water-skin permeation (log ), binding to human plasma proteins (log ), and intestinal permeability (Caco-2), for three classes of fused azaisocytosine-containing congeners that were considered and tested as promising drug candidates. The compounds were characterized by lipophilic, structural, and electronic descriptors, i.e., chromatographic retention, topological polar surface area, polarizability, and molecular weight. Different reversed-phase liquid chromatography techniques were used to determine the chromatographic lipophilicity of the compounds that were tested, i.e., micellar liquid chromatography (MLC) with the ODS-2 column and polyoxyethylene lauryl ether (Brij 35) as the effluent component, an immobilized artificial membrane (IAM) chromatography with phosphatidylcholine column (IAM.PC.DD2) and chromatography with end-capped octadecylsilyl (ODS) column using aqueous solutions of acetonitrile as the mobile phases. Using multiple linear regression, we derived the statistically significant quantitative structure-activity relationships. All these QSAR equations were validated and were found to be very good. The investigations highlight the significance and possibilities of liquid chromatographic techniques with three different reversed-phase materials and QSARs methods in predicting the pharmacokinetic properties of our important organic compounds and reducing unethical animal testing.
定量构效关系（QSAR）方法被用于预测三种融合的含有氮杂胞嘧啶的同系物的生物性质，即血脑分配系数（log ）、脑内未结合分数（）、水皮渗透系数（log ）、与人血浆蛋白的结合（log ）和肠道通透性（Caco-2），这些同系物被认为是有前途的药物候选物并进行了测试。这些化合物的特征是具有亲脂性、结构和电子描述符，即色谱保留、拓扑极性表面积、极化率和分子量。不同的反相液相色谱技术被用于确定所测试化合物的色谱亲脂性，即胶束液相色谱（MLC）与 ODS-2 柱和聚氧乙烯月桂醚（Brij 35）作为流出物成分，固定化人工膜（IAM）色谱与磷脂酰胆碱柱（IAM.PC.DD2）和使用乙腈水溶液作为流动相的端封十八烷基硅烷（ODS）柱的色谱。通过多元线性回归，我们得出了具有统计学意义的定量构效关系。所有这些 QSAR 方程都经过了验证，结果非常好。这些研究强调了使用三种不同反相材料和 QSAR 方法的液相色谱技术在预测我们重要有机化合物的药代动力学性质和减少不道德的动物测试方面的重要性和可能性。
