Computational Study of Coumarin Compounds as Potential Inhibitors of Casein Kinase 2: DFT, 2D-QSAR, ADMET and Molecular Docking Investigations

Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, there has been a notable increase in interest in the use of casein kinase 2 (CK2) inhibitors to improve the treatment of a specific form of cancer while minimizing the risk of undesirable side effects. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that the coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, quantitative structure-activity relationship (QSAR) analysis has been employed to envisage the inhibitory effects of 32 coumarin derivatives on the CK2 protein. The most efficient model is found by using multiple linear regression (MLR). Its capability is considered by the external and internal validation values found (R² = 0.884, Q2cv = 0.822, R²pred = 0.821, and R²p = 0.811), which aligned well with Tropsha and Golbraikh’s approach. The highest docking score founded for the newly designed coumarins is −7.50 kcal mol-1, which indicates that candidates can bind to the CK2 receptor with greater affinity. Based on the results of the ADMET properties and drug similarity analyses, a DFT investigation was conducted to confirm the stability of the newly explored compounds. It appears that the most stable complexes are those of compound with the highest binding affinity with a lower risk of toxicité.