Unlocking the therapeutic potential of Origanum majorana through GC-MS and computational analysis to identify EGFR inhibitors for breast cancer.

Triple-negative breast cancer (TNBC) remains a significant clinical challenge due to its resistance to conventional treatments and the well-established role of epidermal growth factor receptor (EGFR) as a critical molecular target. This study explores the potential of Origanum majorana, a Mediterranean herb, as a source of natural EGFR inhibitors. The essential oil from Saudi Arabian O. majorana aerial parts was extracted and profiled using Gas Chromatography-Mass Spectrometry (GC-MS), identifying the major constituents. Predominant compounds were virtually screened against the EGFR tyrosine kinase domain via molecular docking and docking poses were validated. Subsequent molecular dynamics simulations together with MM-GBSA free energy analysis indicated that limonene formed the most stable complex with EGFR, exhibiting minimal structural deviation and consistent hydrophobic contacts. Density Functional Theory (DFT) analysis characterized limonene's electronic stability and hydrophobic nature, which underpin its binding mechanism. ADME predictions indicated limonene's favorable drug-likeness and blood-brain barrier permeability. This integrated approach identifies limonene as a promising natural scaffold for EGFR inhibition, warranting further experimental validation for its potential advancement as a treatment option for breast cancer.