Synthesis and EGFR binding evaluation of various substituted aurones via molecular docking approaches

Aurones, belonging to the flavonoid family and widely distributed in various plant species, have attracted significant attention due to their potential inhibitory effects on the epidermal growth factor receptor (EGFR). In this study, a series of substituted aurones was synthesized through the oxidative cyclization of chalcones. Molecular docking studies were conducted using Autodock Vina to evaluate the binding interactions between these aurones and the EGFR kinase domain. The results indicate that aurone derivatives effectively bind to the EGFR active site, with fluorine-substituted aurones (particularly compound 4o) displaying superior binding affinity compared to bromine- and chlorine-substituted analogues. Additionally, methyl-substituted aurones (4a and 4b) exhibited the highest binding affinity of -8.4 kcal/mol. The reliability and stability of the EGFR tyrosine kinase protein model used in the docking studies were validated by the Ramachandran plot analysis. These results support aurone derivatives-especially fluorine- and methyl-substituted scaffolds-as promising EGFR binders with favorable drug-likeness, warranting targeted biochemical validation.