2D-QSAR, Molecular Docking, and in silico Pharmacokinetics Analysis on N-substituted Urea and Thiourea Derivatives as Tankyrase Inhibitors for Implication in Cancer

Objectives: Cancer is among four major Non-Communicable Diseases (NCD). Based on the World Health Organization (WHO), it is the biggest cause of mortality globally, claiming about 10 million lives in recent years. Tankyrases is a poly polymerase (ADP-ribose) family enzyme, inhibiting its enzymatic processes plays a crucial part in cancer etiology. Materials and Methods: The Algorithm of Kennard-Stone was utilized to develop QSAR models of thirty-four cytotoxic compounds of N-naphthoyl thioureas and N-aryl-N'-benzylurea using the multiple linear regression approach. 2D QSAR best models were developed and the finest model was selected using statistical reliability (R2) of 0.9253, (R2 adj) of 0.9045, (Q2 cv) cross-validation coefficient of 0.8767, and (R2test) of 0.6015. Results: The R2 value of 0.9253 shows the model is promising by indicating 92.53% of the residual deviation, and this model was not over-fitted, as seen by how near Q2 cv is to internal R2. The molecular docking studies were conducted between some selected compounds (based on activity) and Tankyrases protein receptors to investigate the binding modalities and ADMET was also conducted to determine their oral bioavailability. Three compounds C18, C25, and C33 showed favourable interaction and good binding energy and were consistent with drug-likeness parameters. Furthermore, the crystal structure of the compounds bound to Tankyrases protein receptors has yet to be confirmed experimentally. Conclusion: Thus this article provides insight into the residual interaction between these compounds and Tankyrases protein receptors.