QSAR modeling, docking, ADME and reactivity of indazole derivatives as antagonizes of estrogen receptor alpha (ER-α) positive in breast cancer

To establish a quantitative structure-activity relationship, 54 indazole derivatives were analyzed by multiple linear regression MLR. The DFT-B3LYP method, with the basis set 6-311G, was performed to define the structure, chemical reactivity and properties of the compounds. This study was accompanied by molecular docking, global reactivity descriptors, absorption, distribution, metabolism and elimination (ADME) properties on a series of 21 compounds of selective estrogen receptor degraders (SERDs) that present the most active compounds from the dataset. The MLR regression equation displayed a good agreement between fitted and observed biological activities. A high average R2Boots greater than 0.5 indicates that the obtained model has good predictive power and robustness. In addition, an average value of R2pred (0.57) approximately equal to 0.6 may be taken as an indicator of good external predictability. The interactions between the most active compounds from the indazole series and ERα targets were explored through a molecular docking to elucidate the binding mode between the studied compounds and corresponding protein. Based on this study compounds 14, 43, 8 and 45 have no violated Lipinski’s rule of five and Veber’s rule, suggesting that these compounds would not have problems with oral bioavailability. Most of global reactivity results have an agreement with those obtained in this docking study.