What question did this study set out to answer?

The aim is to design and synthesize novel benzimidazole derivatives and evaluate their antitumor mechanisms against cancer cell lines.

January 23, 2026Open Access

Design, synthesis, and preliminary antitumor mechanism of benzimidazole derivatives

Puntos clave

The aim is to design and synthesize novel benzimidazole derivatives and evaluate their antitumor mechanisms against cancer cell lines.
Synthesis of fourteen benzimidazole derivatives
Evaluation of antitumor activities using MTT assay against four cancer cell lines
Flow cytometry analysis to study apoptosis and cell cycle effects
Western blot analysis to examine protein expression changes
Molecular docking to assess binding affinity with BCR-ABL protein
Compound E12 showed the highest activity against K562 cells with an IC50 of 11.07 μM
E12 exhibited low toxicity to normal HEK-293 cells with an IC50 greater than 40 μM
E12 induced apoptosis and increased levels of reactive oxygen species
E12 caused cell cycle arrest in the G2/M phase
Molecular docking indicated strong binding of E12 to BCR-ABL with a binding energy of -9.3 kcal/mol

Resumen

Fourteen novel benzimidazole derivatives were designed, synthesized, and evaluated for their antitumor activities against four human cancer cell lines, A549 (lung carcinoma), 5637 (bladder cancer), PC-3 (prostate cancer), and K562 (chronic myelogenous leukemia- CML), using the MTT assay. Among these, compound E12 demonstrated the most potent activity against the K562 cells, exhibiting significant growth inhibition with an IC 50 value of 11.07 μM, while demonstrating low toxicity towards the normal HEK-293 (embryonic kidney) cell line, with an IC 50 greater than 40 μM. Flow cytometry analysis revealed that E12 induced apoptosis, increased reactive oxygen species levels, decreased mitochondrial membrane potential, and caused cell cycle arrest at the G2/M phase. Additionally, western blot analysis showed that E12 effectively inhibited BCR-ABL expression, upregulated Bax expression, and downregulated Cyclin B1 and CDK-1 expression to induce apoptosis. Molecular docking results also showed that compound E12 had a strong binding ability with the BCR-ABL protein, and the binding energy was -9.3 kcal/mol. These findings suggest that E12 is a promising candidate for further development as an anti-chronic myeloid leukemia drug.

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