In Silico Investigation, Synthesis, Spectroscopic Characterization, Molecular Docking, and ADME Analysis of a Anthracene-Based Chalcone Targeting EGFR Tyrosine Kinase

A anthracene-based chalcone, (E)-3-(anthracen-9-yl)-1-(4-fluorophenyl)prop-2-en-1-one, was successfully synthesized via a Claisen–Schmidt condensation reaction between 4-fluoroacetophenone and anthracene-9-carbaldehyde under alkaline conditions. The synthesized compound was purified by recrystallization and structurally characterized by ¹H NMR, and ¹³C NMR spectroscopy, confirming the successful formation of the α,β-unsaturated carbonyl framework. To evaluate its potential as an anticancer agent, molecular docking studies were performed against the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase domain (PDB ID: 1M17). The synthesized chalcone exhibited a remarkable binding affinity with a docking score of −10.3 kcal mol⁻¹, indicating strong interaction within the ATP-binding pocket of the receptor. The ligand established stable π-sigma, π-sulfur, and π-alkyl interactions with key amino acid residues, including Leu820, Met742, Ala719, Val702, Lys721, and Arg817, which contribute significantly to the stability of the protein–ligand complex and suggest its potential as an EGFR tyrosine kinase inhibitor. Furthermore, SwissADME analysis was carried out to predict the pharmacokinetic and drug-likeness properties of the synthesized compound. The molecule demonstrated favorable membrane permeability, moderate oral bioavailability (bioavailability score = 0.55), indicating a low probability of false-positive biological activity. However, its high lipophilicity, poor aqueous solubility, low predicted gastrointestinal absorption, and P-glycoprotein substrate characteristics may limit oral bioavailability and require further structural optimization. This combined synthetic, spectroscopic, molecular docking, and ADME investigations demonstrate that the synthesized anthracene-based chalcone represents a promising lead scaffold for the development of novel EGFR-targeted anticancer agents, warranting further biological evaluation and structural refinement.