Synthesis of Novel Triazole Substituted Benzimidazole Libraries and Evaluation of Their Anticancer Activity

The development of novel heterocyclic hybrids with potent and selective anticancer activity remains an important challenge in medicinal chemistry, particularly because the generation of structurally diverse scaffolds with efficient synthetic accessibility and promising biological profiles remains technically demanding. In this context, we report an efficient synthesis of a new library of benzimidazole–1,2,3-triazole derivatives (5a–k) and their acylhydrazone analogues (7a–h) from propargyl alcohol through a sequential click reaction, oxidation, condensation, and rearrangement strategy under mild conditions. The key innovation of this work lies in integrating these sequential transformations into a practical synthetic route that enables the generation of structurally diversified benzimidazole–triazole-based architectures and their acylhydrazone derivatives. In addition, the synthesized compounds anticancer activity was evaluated against A549, HeLa, and MDA-MB-231 human cancer cell lines. Several compounds, particularly 5b, 5c, 5 g, 5h, 7c, and 7h, exhibited potent anticancer activity with IC50 values ranging from 0.14 to 0.66 μM. These activities were comparable to those of reference drugs, indicating the therapeutic potential of the benzimidazole–triazole scaffold. This study demonstrates a practical synthetic approach to novel benzimidazole–triazole hybrids and identifies promising lead molecules for further anticancer drug development.