MOLECULAR DOCKING OF QUERCETIN DERIVATIVES AGAINST EGFR IN NON–SMALL CELL LUNG CANCER (NSCLC)
DOI:
https://doi.org/10.36526/jc.v8i2.7202Keywords:
Docking Molecular, ADMET, EGFR, NSCLC, Quercetin DerivativesAbstract
Non – small cell lung cancer (NSCLC) is leading cause of cancer – related mortality. Resistance to existing epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors remains a major therapeutic challenge. This study investigates the potential of thirteen 8 – heteroarylated quercetin derivatives as EGFR inhibitors using a structure – based molecular docking approach integrated with in silico ADMET prediction and drug – likeness assessment. Docking simulations were performed against EGFR (PDB ID: 4WKQ) using MOE 2022, with gefitinib serving as the reference ligand. ADMET evaluation was conducted using the pkCSM web server, while drug – likeness assessment was carried out using SwissADME. The docking results revealed that five compounds (2i, 2b, 2m, 2a, and 2c) exhibited more favorable binding affinity than the control and formed key hydrogen – bond interactions with resiude Met793, along with additional interactions within the ATP – binding site. ADMET and drug – likeness analyses predicted that most derivatives complied with Lipinski’s criteria, with compounds 2a and 2m demonstrating superior pharmacokinetic profiles, including higher solubility, acceptable intestinal permeability, low blood – brain barrier penetration, and low predicted acute toxicity and mutagenicity. Overall, these in silico findings identify compounds 2a and 2m as the most promising quercetin – based EGFR inhibitor candidates for futher development.
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