2-(3-R-1,2,4-triazol-5-yl)anilines; tyrosine kinase inhibitors; molecular docking; non-small cell lung cancer; antitumor agents.


The present work is devoted to the in silico study of 2-(3-R-1H-1,2,4-triazol-5-yl)anilines as potential inhibitors of EGFR (epidermal growth factor receptor) and RET (rearranged during transfection)-, which play a significant role in regulating the physiological cycle of non-small cell lung cancer. The well-known docking software AutoDock Vina was used for the study. The seven studied compounds and two standard drugs (vandetanib and gefitinib) were docked to the crystal structures of EGFR and RET proteins. It was found that among the newly investigated substances, 2-(3-(indolyl-2)-1H-1,2,4-triazol-5-yl)aniline (a5) has the highest affinity towards EGFR and RET with the binding energy of 9.7 and –8.7 kcal/mol, respectively. Visualization of the molecular docking results of this compound using the Discovery Studio software showed that it is characterized by similar to standard ligands location in the active sites of the enzymes, stable hydrogen bonds and π-stacking interactions, which are provided by the presence of indole and aniline fragments in the molecule. Thus, we have identified a new effective ligand that can be used as a "base" molecule for further fragment-oriented design using molecular hybridization methodology (fragment fusion, coupling or extension methods) or structural modification by introducing "pharmacophore" groups into the molecule. Summarizing the above screening results, we can say that 2-(3-R-1H-1,2,4-triazol-5-yl)anilines require further careful consideration as effective tyrosine kinase inhibitors for the search for promising anticancer agents for the treatment of non-small cell lung cancer.


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