Isolation, characterization, and biological evaluation of endophytic fungi from Phragmites australis: experimental and computational insights

Endophytic fungi are an uncharted source of bioactive metabolites with varied therapeutic characteristics. In this research, an endophytic <i>Aspergillus</i> sp. (HAG1) was collected from <i>Phragmites australis</i> and identified using morphological and molecular methods. The large-scale fermentation, chromatographic purification, and spectroscopic approaches (FT-IR, UV-Vis, ¹H NMR, and ESI-MS) resulted in the identification of three metabolites: vaccenic acid (<b>C1</b>), pipericine (<b>C2</b>), and guaiacylglycerol (<b>C3</b>). Of these, <b>C3</b> is reported here for the first time as an endophyte-derived metabolite from <i>P. australis</i>. All the metabolites exhibited significant antioxidant, antibacterial, antibiofilm, and anti-inflammatory activity. The activities of <b>C3</b> were the most effective in DPPH and ABTS scavenging, COX-1/COX-2 inhibition, and suppression of biofilm for bacteria, although <b>C3</b> was inactive against acetylcholinesterase activity. Molecular docking and molecular dynamics (MD) simulations underscored a favorable binding with a high binding conformation stability of <b>C3</b> for antioxidant (1DGF), anti-inflammatory (3NLO), and antibiofilm (5TZ1) targets. In addition, density function theory (DFT) calculations delivered insights regarding electronic structure, explaining observed reactivity and hydrogen bonding ability. Moreover, ADMET predictions indicated that <b>C3</b> has favorable solubility, metabolic stability, and low toxicity when compared to <b>C1</b> and <b>C2</b>.