N (4‐(1h‐Benzimidazol‐2‐yl) Phenyl)‐2‐Aminoacetamide: Synthesis, Docking, In Silico ADME Prediction and Evaluation for Anticancer Activity

ABSTRACT To discover an anticancer drug and expand our research scope, a novel series of benzimidazole phenyl acetamide derivatives (3a–j) was designed and synthesized. All the synthesized derivatives ( 3a–j ) were characterized and confirmed using modern spectroscopic techniques and evaluated for in vitro cytotoxicity via the SRB assay against two cancer cell lines, namely MCF‐7 (breast cancer) and A549 (lung cancer). The 5‐Fluorouracil and Adriamycin were used as standards. The Compounds 3a, 3i, and 3j exhibited good anticancer activity against the A549 cancer cell line with GI 50 values of 40, 20, and 10 µM, respectively. However, this series of compounds was found to be less active against the MCF‐7 cell line, except for Compound 3j, which exhibited a GI 50 value 30 µM . The molecular docking studies of all the designed derivatives (3a–j) , exhibited good binding affinity toward epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor‐2 (VEGFR‐2) tyrosine kinases. Furthermore, MD simulation demonstrates that Complexes 1 and 2 (EGFR–3j and VEGFR‐2–3j) maintain superior structural stability and compactness compared to the reference complex (VEGFR‐2–Dovitinib) , underscoring the strong and stable binding potential of the synthesized Compound 3j with both target proteins. Upon the in silico bioavailability studies for all the synthesized derivatives (3a–j), they displayed favorable drug‐like properties.