Design, Synthesis, and Biological Evaluation of Novel Benzimidazole/Schiff Base Hybrid Derivatives With Potential Biological Activities
A novel series of benzimidazole‐based derivatives (5a–g), (6a–b), and (7a–b) were designed, synthesized, and evaluated for their potential as dual inhibitors of EGFR and HER‐2. The synthesized compounds were subjected to in vitro screening against a panel of selected human cancer cell lines. Additionally, their cytotoxicity was assessed using normal human mammary epithelial cells (MCF‐10A) to evaluate their safety profile. Among the tested derivatives, compounds 5b, 5f, and 6a demonstrated the most pronounced antiproliferative activity, exhibiting IC₅₀ values of 6, 8, and 5 μM, respectively. These values reflect a potency at least fourfold greater than that of the reference drug doxorubicin (IC₅₀ = 33 μM). EGFR and HER‐2 enzyme inhibition assays were conducted to explore the potential molecular targets responsible for the observed anticancer effects. Notably, compound 6a (R₁ = phenyl, thiosemicarbazide) exhibited superior efficacy against the MCF‐7 breast cancer cell line, with an IC₅₀ of 5 μM, approximately six times more potent than doxorubicin. Conversely, compound 7b, with an IC₅₀ value of 85 μM against MCF‐7 cells, was the least active, underscoring the critical role of the phenyl moiety in antiproliferative activity. Furthermore, a molecular docking study was conducted to investigate the binding interactions of 6a within the active sites of EGFR and HER‐2, providing insight into its potential mechanism of action.
