DOI: 10.65520/erciyesfen.1927513 ISSN: 1012-2354

Molecular Docking Analysis of Quinazoline Derivatives Against EGFR Tyrosine Kinase: An In Silico Study Comparative with Erlotinib

Medine Karadağ Alpaslan
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Background/Aim: Cancer is one of the leading causes of morbidity and mortality worldwide. Epidermal growth factor receptor (EGFR) is attracting attention as an important therapeutic target in many types of cancer. The aim of this study is to evaluate the binding affinity and interaction profiles of selected quinazoline derivatives against the EGFR tyrosine kinase domain using molecular docking analysis.Methods: In this study, the binding potential of three quinazoline compounds (CID: 24945791, 1474881, and 14022362) selected from the PubChem database to the EGFR tyrosine kinase domain was evaluated using molecular docking, and the results were compared with those of the reference inhibitor Erlotinib.Results: According to the docking results, compound CID: 24945791 was determined as the ligand of the highest affinity, with a binding energy of -8.11 kcal/mol. The hydrogen bonds formed by this compound with PRO770 and MET769, the π-cation interaction with LYS721, and the intense π-alkyl interactions with hydrophobic amino acids significantly contribute to its binding stability. Compound CID:1474881 exhibits a moderate binding affinity with a binding energy of -7.32 kcal/mol and is stabilized in the active site by multiple hydrogen bonds and hydrophobic interactions. In contrast, compound CID:14022362 was identified as the ligand with the lowest affinity, with a binding energy of -5.67 kcal/mol, and the steric overlap observed with CYS751 negatively affected its binding stability.Conclusion: These findings indicate that quinazoline derivatives have potential as EGFR inhibitors, and compound CID:24945791, in particular, could be a strong candidate. This study provides an in silico basis for the development of next-generation EGFR inhibitors.

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