Design and synthesis of new heterocyclic compounds containing 5-[(1-1,2,4-triazol-1-yl)methyl]-3-1,2,4-triazole-3-thione structure as potent hEGFR inhibitors.

EGFR is one of the important mediators of the signaling cascade that determines key roles in various biological processes such as growth, differentiation, metabolism and apoptosis in the cell in response to external and internal stimuli. In recent years, it has been proven that although this enzyme activity is tightly regulated in normal cells, if the enzyme activity cannot be controlled, it can lead to malignancy. EGFR is also considered a prominent macromolecule in targeted cancer chemotherapy. For this purpose, a comprehensive modeling studies were conducted against EGFR protein and novel molecules containing 5-[(1-1,2,4-triazol-1-yl)methyl]-3-1,2,4-triazole-3-thione structure were suggested to be synthesized. Among the synthesized molecules, compounds , , and were determined to have significant IC values. Compound was found to have the IC value closest to the very well-known EGFR inhibitor Gefitinib with its noncompetitive inhibition form. value of compound was calculated as 0.00232 µM.Communicated by Ramaswamy H. Sarma.