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Published: 2025-01-20

Keywords:Design, Synthesis, In-silico Molecular Docking, ADMET Analysis, and In-Vitro Cytotoxicity Assay of (Z)-N-(4-(1H-benzo[d]imidazol-2-yl)phenyl) Derivatives for EGFR Inhibition

ABSTRACT

Epidermal Growth Factor Receptor (EGFR) inhibition is a promising strategy in cancer treatment. This study aimed to design, synthesize, and evaluate novel (Z)-N-(4-(1H-benzo[d]imidazol-2-yl)phenyl) derivatives as potential EGFR inhibitors with anticancer activity. Thirty compounds were designed and analyzed for drug-likeness using Lipinski's rule and Veber's criteria. Molecular docking simulations with EGFR were performed using AutoDock Vina. Selected compounds were synthesized and characterized by FTIR, 1H NMR, 13C NMR, and MS. Twenty-three compounds fully complied with Lipinski's rule. Docking scores ranged from -6.9 to -9.1 kcal/mol, with Sa8 (-9.1 kcal/mol), Sa4 (-8.8 kcal/mol), and Sa30 (-8.8 kcal/mol) outperforming Erlotinib (-8.1 kcal/mol). These compounds formed key interactions with residues including PHE723, LEU718, and ASP855. This study identified three promising (Z)-N-(4-(1H-benzo[d]imidazol-2-yl)phenyl) derivatives (Sa8, Sa4, Sa30) as potential EGFR inhibitors with significant anticancer activity. The strong correlation between computational predictions and experimental results validates the integrated approach, providing a foundation for further optimization of these lead compounds for enhanced EGFR inhibition and anticancer efficacy.