Department of Chemistry, Erciyes University, Kayseri, Turkey.
SAR QSAR Environ Res. 2012 Jul;23(5-6):409-33. doi: 10.1080/1062936X.2012.665082. Epub 2012 Mar 27.
In this work, the EC-GA method, a hybrid 4D-QSAR approach that combines the electron conformational (EC) and genetic algorithm optimization (GA) methods, was applied in order to explain pharmacophore (Pha) and predict anti-HIV-1 activity by studying 115 compounds in the class of 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio) thymine (HEPT) derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs). The series of NNRTIs were partitioned into four training and test sets from which corresponding quantitative structure-activity relationship (QSAR) models were constructed. Analysis of the four QSAR models suggests that the three models generated from the training and test sets used in previous works yielded comparable results with those of previous studies. Model 4, the data set of which was partitioned randomly into two training and test sets with 11 descriptors, including electronical and geometrical parameters, showed good statistics both in the regression (r2(training) )= 0.867, r2test = 0.923) and cross-validation (q (2) = 0.811, q2(ext1) = 0.909, q2(ext2) = 0.909) for the training set of 80 compounds and the test set of 27 compounds. The prediction of the anti-HIV-1 activity of HEPT compounds by means of the EC-GA method allowed for a quantitatively consistent QSAR model. In addition, eight novel compounds never tested experimentally have been designed theoretically using model 4.
在这项工作中，应用了 EC-GA 方法，这是一种将电子构象（EC）和遗传算法优化（GA）方法相结合的混合 4D-QSAR 方法，以便通过研究 115 种作为非核苷逆转录酶抑制剂（NNRTIs）的 1-[(2-羟乙氧基）-甲基]-6-（苯硫基）胸腺嘧啶（HEPT）衍生物类化合物来解释药效团（Pha）并预测抗 HIV-1 活性。NNRTIs 系列化合物被分为四个训练集和测试集，从这些集合中构建了相应的定量构效关系（QSAR）模型。对四个 QSAR 模型的分析表明，从先前工作中使用的训练集和测试集中生成的三个模型与先前研究的结果具有可比性。模型 4 的数据集是通过随机将其分为两个训练集和测试集得到的，包含电子和几何参数等 11 个描述符，对于 80 个化合物的训练集和 27 个化合物的测试集，在回归（r2(training)=0.867，r2test=0.923）和交叉验证（q (2)=0.811，q2(ext1)=0.909，q2(ext2)=0.909）方面均显示出良好的统计学效果。通过 EC-GA 方法预测 HEPT 化合物的抗 HIV-1 活性，得到了一个定量一致的 QSAR 模型。此外，还使用模型 4 理论上设计了从未经过实验测试的八种新型化合物。
