UREA AND THIOUREA DERIVATIVES AS AN ENDOTHELIAL GROWTH FACTOR RECEPTOR AND HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 INHIBITORS MOLECULAR DOCKING STUDIES

Abstract

Using molecular docking we evaluate the binding mode, interaction and inhibition potential of urea and thiourea derivatives against EGFR and HER-2. The result of molecular docking shows that the urea derivatives (U₁-U₄)possess high binding energies against EGFR having -9.62 kcal/mol, -10.15 kcal/mol, -10.03 kcal/mol and -10.31 kcal/mol respectively. Similarly urea derivative (U₁-U₄) shows the binding energies value of -11.33 kcal/mol, -11.09 kcal/mol, -12.11 kcal/mol and -11.23 kcal/mol respectively against HER-2. Thiourea derivatives against EGFR shows the binding energies -9.90 kcal/mol, -10.17 kcal/mol, -11.07 kcal/mol and -10.13kcal/mol of compounds (T₁-T₄) respectively. Thiourea derivatives like (T₁-T₄) show the binding energies value of -10.37kcal/mol, -10.71 kcal/mol,-10.79 kcal/mol and -10.72kcal/mol respectively against HER-2. All compounds show high inhibitory properties against EGFR and HER-2 proteins which is comparable to the binding energies values of standard (Sorafenib and Regorafenib) These inhibitors compounds like urea and thiourea derivatives are shows good results and can be used for the treatment of breast cancer due to their capacity for the successfully modification of the activity of drugs used against breast cancer. There may be powerful EGFR, HER-2 inhibitor with high and improved efficiency and less side effects as a product for further research and evaluation of these drugs. The conclusion obtained from this study is that urea and  thiourea derivatives show better inhibitory activity against selected proteins.