3D-QSAR modeling and molecular docking studies on a series of 2, 4, 5-trisubstituted imidazole derivatives as CK2 inhibitors

Protein case in kinase II alpha subunit (CK2) plays an imperative function in treating cancer disease. Herein, we have performed a three-dimensional quantitative structure activity relationship (3D-QSAR), and molecular docking analysis on a novel series of 2, 4, 5-trisubstituted imidazole derivatives in order to design potent kinase II alpha subunit (CK2) inhibitors. The 3D-QSAR methods such as comparative molecular similarity indexes analysis (COMSIA), and the comparative molecular field analysis (COMFA) were investigate using twenty-four molecules of 2, 4, 5-trisubstituted imidazole derivatives as anticancer agent. The best COMFA and COMSIA models exhibit excellent Q(2) values of 0.66 and 0.75 and R-2 values of 0.98 and 0.99 respectively. To check the validity of the selected COMFA and COMSIA models, a variety of validation tests were utilized: Internal validation analyses, and externally validation beside Y-randomization according to the principles of the Organization for Economic Co-operation and Development (OECD), and the Golbraikh and Tropsha's criteria for the validation of 3D-QSAR models. The proposed models for COMFA and COMSIA analysis have been successful. The developed models, indicating that they were reliable for activity prediction. Based on the preceding results, we designed several new potent molecules. Such outcome can proffer helpful theoretical references for future experimental studies.