Synthesis and Characterization of Novel (Substituted‐Phenyl)‐(5‐Methoxy‐2‐Phenyl‐1H‐1,3‐Benzimidazol‐1‐yl) Methanone Derivatives and Evaluation of Anticancer Activity

A series of 5‐methoxy aryl benzimidazole derivatives were designed and synthesized using a simple two‐step facile method. The novel benzimidazole derivatives were characterized through FT‐IR, 1 H‐NMR, 13 C‐NMR, and LC‐MS. The synthesized compounds ( C1–C9 ) were screened for their in vitro anticancer activity against MCF‐7 (human breast adenocarcinoma), HeLa (cervical cancer), and A549 (non–small‐cell lung carcinoma) cell lines using cell viability assays. These cell lines exhibit high basal surface expression of EGFR, the cytotoxic effects were evaluated over a broad concentration range (0.625 to 300 µg/mL), and the IC 50 values were determined. Doxorubicin was used as a standard reference drug for comparison. In the designed 5‐methoxy aryl benzimidazole derivatives, C1 and C7 were the top hits in molecular docking. They had better interaction than the standard reference, with interaction energies of −9.280 and −9.250 kcal/mol, respectively. They had hydrogen bond interactions with THR798 and MET801 at the ATP‐binding site of EGFR kinase. Among the tested compounds, C7 and C1 demonstrated significant anticancer activity, showing potent growth inhibition with an IC50 value of 9.2 ± 0.5 µM against the MCF‐7 cell line, highlighting its potential as a strong candidate for breast cancer therapy. Similarly, Compound C1 demonstrated notable potency against the A549 cell line, with an IC50 value of 16.6 ± 2.3 µM. These novel 5‐methoxy aryl benzimidazole derivatives exhibited potent anticancer activity.