Structure-based identification of natural EGFR modulators from Codariocalyx motorius using computational approaches

The epidermal growth factor receptor (EGFR) is a transmembrane protein that plays a pivotal role in cellular signaling. EGFR dysregulation is critically associated with oncogenic signaling cascade, establishing it as a prime target for cancer therapeutics. However, the emergence of drug resistance continues to limit the long-term effectiveness of EGFR inhibitors. The present study investigates the phytochemicals of the medicinal plant, Codariocalyx motorius , known for its broad therapeutic potential, as a source of potent EGFR modulators. Initially, the phytochemicals of the plant were identified through literature analysis. Later, molecular docking, drug-likeness predictions, molecular dynamics simulations, and MM/PBSA-based binding free energy calculations were employed to assess the binding affinity of these compounds against EGFR. Among the 26 screened compounds, 24 showed higher docking scores than the reference drug Gefitinib. Among these, Apigenin-7-O-glucuronide and Scutellarein-6-O-glucuronide demonstrated stronger binding affinities than the control drug Erlotinib. Notably, Apigenin-7-O-glucuronide showed the most promising therapeutic potential, as evidenced by its favorable binding mode, interactions with key amino acid residues, stable binding conformations, compact radius of gyration (Rg), and reduced solvent-accessible surface area (SASA). Binding free energy calculations further supported its stable association with the EGFR binding site. Overall, the findings of this study highlight the potential of phytochemicals from Codariocalyx motorius in modulating EGFR activity and suggest Apigenin-7-O-glucuronide as a promising lead compound for further experimental validation for EGFR-targeted cancer therapy.