Target-Oriented Molecular Docking and Admet Analysis of Novel Chalcone-Linked Quinoline Derivatives for Cancer Therapy

Objective: Molecular docking studies were carried out on thirty-three novel chalcone-linked quinoline derivatives to evaluate their potential as anticancer drug candidates targeting EGFR tyrosine kinase. Methods: The computational study was executed using the Maestro interface in the Schrodinger to target EGFR enzyme (PDB ID: 4HJO). For all the compounds, molecular docking was subjected to ADME analysis using QikProp module. Results: Analysis of protein-ligand interactions demonstrated that the most active compounds formed stable hydrogen bonds with key residues PHE-832, THR-830, SER-676, THR-766, MET-796, CYS-751, GLN-767 and ASN-818 in the EGFR binding pocket. ADMET predictions indicated favorable drug-like properties for all compounds, with acceptable molecular weights range of ≤500 Da, optimal lipophilicity (LogP< 5), and high gastrointestinal absorption rates. The compounds showed compliance with Lipinski’s rule of five and exhibited blood-brain barrier permeability. Conclusion: The targeting of EGFR tyrosine kinase by these derivatives indicates potential effectiveness of chalcone linked quinoline derivatives.