Synthesis of Fused 1,2,3-Triazoles of Benzimidazole Using Copper (I) Catalysis; in Vitro and in Silico Studies

In this study, we described the synthesis of some new benzimidazole-1,2,3-triazole hybrids (4a–n) using well-known copper-catalyzed CuAAC and C─H arylation cascade reactions. We validated the structures of all compounds by using ¹H NMR, ¹³C NMR, and mass spectrometry. In vitro assessment of anticancer efficacy against breast cancer cells, such as MCF-7 and MDA-MB-468, demonstrated that compounds 4d, 4e, and 4f had superior activity comparable to the standard drug Erlotinib. Furthermore, compounds 4d, 4e, and 4f have the highest inhibitory efficacy against the tyrosine kinase EGFR, relative to the reference drug Erlotinib. Molecular docking investigations of the effective compounds 4d, 4e, 4f, and 4n with EGFR showed a greater affinity for the target protein. Furthermore, the in silico pharmacokinetic profile of the potent compounds 4d, 4e, 4f, and 4n was determined by using SWISS/ADME and pkCSM, and all the four compounds obeyed Lipinski, Ghose, Veber, Egan, and Muegge guidelines without any variation.