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溶血磷脂酸酰基转移酶-β(LPAAT-β)是肿瘤治疗的新靶点,2-芳基苯并噁唑衍生物是最近发现的LPAAT-β抑制剂,可以选择性抑制LPAAT-β的活性,从而抑制肿瘤细胞的增殖。本文运用比较分子力场分析(CoMFA)建立了2-芳基苯并噁唑LPAAT-β抑制剂的三维定量构效关系(3D-QSAR)模型,考察了网格步长对模型的影响。优化后的模型交叉验证系数q~2=0.626,最佳主成分数为3,传统的相关系数r~2=0.933,统计方差比F=102.391。该模型对训练集和测试集化合物进行预测,预测值和实验值非常接近,表明模型具有很好的预测能力。该模型显示立体场和静电场对生物活性的贡献分别为59.5%和40.5%。CoMFA模型的三维等值图可为改造化合物结构提供理论依据。
Lysophosphatidic acid acyltransferase-β (LPAAT-β) is a new target for cancer therapy. 2-Arylbenzoxazole derivatives are the newly discovered LPAAT-β inhibitors that selectively inhibit the activity of LPAAT-β , Thereby inhibiting the proliferation of tumor cells. In this paper, a 3D-QSAR model of 2-arylbenzoxazole LPAAT-β inhibitors was established by using comparative molecular force field analysis (CoMFA), and the effect of grid step size on the model was investigated. The optimized model cross-validation coefficient q ~ 2 = 0.626, the best principal component is 3, the traditional correlation coefficient r ~ 2 = 0.933, the statistical variance ratio is F = 102.391. The model predicts the training set and the test set compounds. The predicted value is close to the experimental value, indicating that the model has good predictive ability. The model shows that the contribution of stereo and electrostatic fields to biological activity is 59.5% and 40.5%, respectively. The three-dimensional contour of CoMFA model can provide a theoretical basis for the transformation of compound structure.