Keywords:Epidermal growth factor receptor (EGFR); AutoDock Vina; Erlotinib; Doxorubicin; Open Babel; Anticancer

ABSTRACT

The epidermal growth factor receptor (EGFR) plays a pivotal role in the pathogenesis and progression of various cancers. Targeted inhibition of EGFR kinase activity using small molecules is a promising strategy in anticancer therapy. In the present study, molecular docking simulations were performed to evaluate the binding affinity and interaction profiles of a series of synthetic ligands (2a–2h) with the EGFR kinase domain (PDB ID: 2ITY). The docking was conducted using PyRx 0.8 and AutoDock Vina. Ligand and protein preparation were carried out using Open Babel and AutoDock Tools 4.2.6. The binding energies and key interactions were compared with standard drugs, Erlotinib and Doxorubicin. Among the synthesized ligands, compound 2b exhibited the highest binding affinity (-7.9 kcal/mol), closely approaching the standard Doxorubicin (-8.3 kcal/mol). All test ligands demonstrated interactions with key residues ASP855 and LYS745 via hydrogen bonding. This suggests that these novel ligands, especially 2b, could serve as potential EGFR inhibitors for further anticancer development.