Integrated in silico and experimental evaluation of ergosterol from Pleurotus membranaceus against lung cancer

Abstract

The exploration of edible mushrooms as sources of bioactive compounds has gained significant attention for their potential role in disease prevention and functional food development. In this study, the phytochemical profile and therapeutic potential of Pleurotus membranaceus (PM) against lung cancer-associated targets were evaluated using integrated in silico and experimental approaches. Gas chromatography-mass spectrometry (GC–MS) analysis identified 23 bioactive constituents, among which ergosterol demonstrated promising therapeutic relevance. Molecular docking analyses revealed that ergosterol exhibited a higher binding affinity (− 9.258 kcal/mol) than the standard anticancer drug Erlotinib (− 8.86 kcal/mol) toward key lung cancer-related targets, including PIM1, HIF1, PI3Kα, and receptor tyrosine kinases (RTKs). Molecular dynamics simulations further supported the structural stability of the ergosterol–PIM1 complex through favourable non-covalent interactions, lower RMSD values, and stable radius of gyration (Rg) profiles relative to the reference drug. These findings suggest that ergosterol derived from Pleurotus membranaceus may represent a promising natural bioactive compound for further investigation as a potential therapeutic candidate against lung cancer.