3D-QSAR study and molecular design of anti-proliferative activity for pefloxacin isoriazole sulfide derivatives to human leukemia cells

Based on the Comparative Molecular Field Analysis (CoMFA) method, three dimensional Quantitative Structure-Activity Relationships (3D-QSAR) between the molecular structures and the in vitro anti-proliferative activity (pM) of 24 pefloxacin isotriazole sulfide derivatives against Human leukemia cells (HL60) were established. Twenty compounds in the training set were served to build the predicting models, and the test set of ten compounds (containing template molecule 22 and newly designed 5 molecules) were used to validate the models. The coefficients of the cross-validation (R_cv²) and non cross-validation (R²) for CoMFA model established in this study were 0.436 and 0.903, respectively. The results showed that the model had better statistical stability and predictive ability. In this model, the contributions of the steric and electrostatic fields were 71.8% and 28.2%, respectively, indicating that the main factor to impact on pM were the electronegative substituted groups of small volume was introduced at the 3,4- position of the benzene ring. Base on the CoMFA contour maps, we also designed five novel molecules with satisfied prediction activity for the further experimental validation.