QSAR modeling, molecular docking studies and ADMET prediction on a series of phenylaminopyrimidine-(thio) urea derivatives as CK2 inhibitors

Abstract

In this work, QSAR studies have been carried out on 31phenylaminopyrimidine-(thio) urea derivatives, acting as anticancer agents using by the density functional theory (DFT) method. Quantum chemical descriptors were calculated using B3LYP method, with the basis set 6-31 G.The dataset was at random divided into training and test sets comprising 23 and 8 compounds, respectively in order to attain robust and reliable QSAR model. To check the validity of the selected models, a variety of validation tests were utilized: Internal validation analyses, and externally validation beside Y-randomization following the principles of the Organization for Economic Co-operation and Development (OECD) and the Golbraikh and Tropsha’s criteria for the validation of QSAR models. The proposed model have been successful Finally, molecular docking analysis was carried out to the most representative compound in data set against protein casein kinase II alpha subunit (CK2) which identified by PDB ID: 4anm, to evaluate its binding affinity, wishing to attain potent anticancer agents in the future.Based on the proposed QSAR model, some novel compounds with higher anti-cancer activities have been theoretically suggested and analyzed by ADMET method. The established model can be helpful theoretical references for novel molecules prior to their synthesis.