Laboratório de Química Medicinal e Computacional, Instituto de Física de São, Carlos, Universidade de São Paulo, Brazil.
Med Chem. 2011 May;7(3):155-64. doi: 10.2174/157340611795564240.
Migrastatin, a macrolide natural product, and its structurally related analogs are potent inhibitors of cancer cell metastasis, invasion and migration. In the present work, a specialized fragment-based method was employed to develop QSAR models for a series of migrastatin and isomigrastatin analogs. Significant correlation coefficients were obtained (best model, q2 = 0.76 and r2 = 0.91) indicating that the QSAR models possess high internal consistency. The best model was then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results (R2 pred = 0.85). The final model and the corresponding contribution maps, combined with molecular modeling studies, provided important insights into the key structural features for the anticancer activity of this family of synthetic compounds based on natural products.
迁移素是一种大环内酯天然产物，及其结构相关的类似物是强效的癌细胞转移、侵袭和迁移抑制剂。在本工作中，采用了一种专门的基于片段的方法来开发一系列迁移素和异迁移素类似物的定量构效关系模型。得到了显著的相关系数（最佳模型，q2 = 0.76 和 r2 = 0.91），表明 QSAR 模型具有较高的内部一致性。然后，使用最佳模型来预测外部测试集的效力，预测值与实验结果吻合良好（R2 pred = 0.85）。最终模型和相应的贡献图谱，结合分子建模研究，为基于天然产物的这类合成化合物的抗癌活性的关键结构特征提供了重要的见解。
