3D-QSAR Studies on the Anti-tumor Activity of N-Aryl-salicylamide Derivatives

In the present work, comparative molecular field analysis (CoMFA) techniques were used to perform three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on the anti-tumor activity (pH(i), i = 1, 2, 3, 4) of N-aryl-salicylamide derivatives against four cancer cell lines, including A549, MCF-7, SGC-7901, and Bel-7402. 12 compounds were randomly selected as the training set to establish the prediction models, which were verified by the test set of 5 compounds containing template molecule. The contributions of steric and electrostatic fields to pH(1), pH(2), pH(3), and pH(4) were 23.8% and 76.2%, 20.1% and 79.9%, 18.7% and 81.3%, and 14.3% and 85.7%, respectively. The cross-validation (R-cv(2)) and non-cross-validation coefficients (R-2) were 0.826 and 0.963 for pH(1), 0.867 and 0.974 for pH(2), 0.941 and 0.989 for pH(3), and 0.797 and 0.961 for pH(4), respectively. The CoMFA models were then used to predict the activities of the compounds, and it was found that the models had strong stability and good predictability. Based on the CoMFA contour maps, some key structural factors responsible for the anticancer activity of the series of compounds were revealed. The results provide some useful theoretical references for understanding the mechanism of action, designing new N-aryl-salicylamide derivatives with high anti-tumor activity, and predicting their activities.