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

Abstract 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 1 H NMR, 13 C 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.