ABSTRACT

The hybrid method of the Electron-Conformational Genetic Algorithm (EC-GA) was used to determine the pharmacophore groups and to estimate anticancer activity in isatin derivatives using a robust 4D-QSAR software (EMRE). To build the model, each compound is represented by a set of conformers rather than a single conformation. The Electron Conformational Matrix of Congruity (ECMC) is composed via EMRE software. Electron Conformational Submatrix of Activity (ECSA) was calculated by the comparison of these matrices. Genetic algorithm was used to select important variables to predict theoretical activity. The model with the best seven parameters produced satisfactory results. The E statistics technique was applied to the generated EC–GA model to evaluate the individual contribution of each of the descriptors on biological activity. The r² and q² values of the training set compounds were found to be 0.95 and 0.93, respectively. Because no previous 4D-QSAR studies on isatin derivatives have been conducted, this study is important in the development of new isatin derivatives. In this study, 27 isatin derivatives whose activities were estimated using the hybrid EC-GA method were also investigated through molecular docking and molecular dynamics simulations for their BCL-2 inhibitory activity.

摘要

电子构象遗传算法 (EC-GA) 的混合方法用于确定药效团组并使用强大的 4D-QSAR 软件 (EMRE) 估计靛红衍生物的抗癌活性。为了构建模型，每个化合物都由一组构象异构体而不是单个构象表示。电子一致性矩阵 (ECMC) 是通过 EMRE 软件组成的。通过这些矩阵的比较计算电子构象活性子矩阵（ECSA）。遗传算法被用来选择重要的变量来预测理论活动。具有最佳七个参数的模型产生了令人满意的结果。E 统计技术应用于生成的 EC-GA 模型，以评估每个描述符对生物活性的个体贡献。这发现训练集化合物的r ²和q ²值分别为0.95和0.93。由于之前没有对靛红衍生物进行过 4D-QSAR 研究，因此这项研究对于开发新的靛红衍生物很重要。在这项研究中，还通过分子对接和分子动力学模拟研究了使用混合 EC-GA 方法估计其活性的 27 种靛红衍生物的 BCL-2 抑制活性。