In Silico Analysis of Phytoconstituents from Ethanolic Extract of Plumeria obtusa as Potential EGFR-Targeting Compounds in Lung Cancer

Abstract

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide, where aberrant epidermal growth factor receptor (EGFR) signaling and activating mutations play a central role in tumor progression. Targeted EGFR inhibition has emerged as an effective therapeutic strategy for the management of EGFR-driven NSCLC. Natural products provide a diverse source of chemical scaffolds that may act as potential anticancer agents. Plumeria obtusa is a medicinal plant reported to contain diverse secondary metabolites with potential pharmacological activities. The present study was designed as a preliminary exploratory investigation of phytoconstituents from the ethanolic extract of P. obtusa and their potential interaction with EGFR. GC–MS profiling tentatively identified 42 chromatographic peaks corresponding to multiple phytochemical constituents. The identified compounds were subsequently subjected to drug-likeness and ADME screening using SwissADME, and selected compounds were evaluated by molecular docking against five experimentally determined EGFR kinase-domain structures (PDB IDs: 1XKK, 2ITX, 2GS6, 3VJO, and 4I23). Among the evaluated compounds, 2-Methoxy-5-phenylbenzoic acid (PubChem ID 17834343) exhibited the most favorable docking scores across the five EGFR structures (−6.2 to −7.1 kcal/mol), whereas 7-Oxabicyclo[4.1.0]heptan-3-ol, 6-(3-hydroxy-1-butenyl)-1,5,5-trimethyl- (PubChem ID 5363777) showed scores ranging from −5.5 to −6.7 kcal/mol. The results indicate that 2-Methoxy-5-phenylbenzoic acid has a comparatively favorable predicted interaction profile with the EGFR kinase domain and may warrant further investigation.