Molecular Docking, Synthesis, Characterization, and Preliminary Cytotoxic Study of Novel 1, 2, 3-Triazole-Linked Metronidazole Derivatives

In this study, five novel 1,2,3-triazole derivatives linked to metronidazole that target EGRR TK in a non-small cell lung tumor were developed. The reaction of metronidazole propargylic ether derivative as terminal alkyne and aryl azide derivatives in the existence of sodium ascorbate and CuSO4.5H2O leads to the synthesis of desirable hybrid molecules (I-V) with anticancer properties. This method is recognized as the Cu-catalyst azide-alkyne cycloaddition. The software for MOE, edition 2015-10, was used for docking experiments, and for predicting cytotoxic activity, the MTT cell viability assay was employed. Both in vitro and docking studies revealed that the recently created substances have significant antitumor efficacy. In contrast to erlotinib, they demonstrated significant differences in potency. Compounds I–V all exhibit IC50 values between 3.2-12.677 μM against the cancer cell line A549 (a non-small lung tumor cell line). Compounds II, III, and IV showed moderate inhibitory activity, whereas Compounds I and V showed the highest inhibitory impact, with 3.21 and 4.1 μM, respectively, as the IC50 values. Based on docking and cytotoxic experiments, compounds I and V were shown to have the strongest inhibitory impact and improved binding energy. They contain biphenyl and benzene sulfonamide, respectively, which are connected to the 1, 2, 3-triazole ring in the para position. This suggests that they are the most promising candidates for use as anticancer medications. The recently synthesized compounds showed cytotoxicity and EGFR tyrosine kinase inhibitory potencies.