Synthesis, Biological Investigation, and Molecular Docking of Novel Benzimidazole‐Hydrazone Hybrids as Potential Anticancer Agent Candidates

In this study, six novel Benzimidazole‐hydrazone derivatives starting from the commercially available 1H‐benzo[d]imidazole‐2‐amine were synthesized, and the molecular structure of the obtained compounds were confirmed by NMR, FTIR and MS spectroscopic techniques. The anticancer activities of the synthesized compounds were investigated against HT29 (Human colon adenocarcinoma) and A549 (Human non‐small cell lung cancer) cancer cell lines using xCELLigence real‐time cell analysis. Cell apoptosis was determined by DNA laddering assay and Annexin V/FITC flow cytometer. Compound 4 c exhibited the best anticancer potency against both cancer cell lines (A549 and HT29) with IC50 values of 0.0019 μM and 0.0093 μM, respectively. Compound 4 c reduced the growth of A549 and HT29 cells in vitro and induced early apoptosis of A549 and HT29 cells. Additionaly, all compounds demonstrated favorable pharmacokinetics properties compared to Paclitaxel (reference compound) and the best docking scores were obtained for compounds 4 e and 4 b among the compounds. Novel Benzimidazole‐hydrazone derivatives were synthesized and their anticancer activities were investigated against HT29 (Human colon adenocarcinoma) and A549 (Human non‐small cell lung cancer) cancer cell lines. Compound 4c exhibited the best anticancer potency against both cancer cell lines (A549 and HT29) with IC50 values of 1.9 nM and 9.3 nM, respectively. Compound 4c reduced the growth, and induced early apoptosis of A549 and HT29 cells. Furthermore, in silico ADMET and molecular docking calculations were performed.