Novel Metabolites of Xylaria thienhirunae SWUF17-44.1 with Biological Activities and Molecular Docking Analysis

The extract of Xylaria thienhirunae SWUF17-44.1 displayed broad-spectrum antimicrobial activity, with higher potency against Gram-positive bacteria than Gram-negative strains. Minimum inhibitory concentration (MIC) values were as low as 0.63 µg/µL for Staphylococcus aureus and 1.25 µg/µL for Bacillus subtilis, whereas higher values were observed for Escherichia coli and Pseudomonas aeruginosa. The extract also inhibited fungal growth, with MICs of 6.25 μg/μL against Candida albicans and C. tropicalis. Strong antioxidant activity was observed (DPPH IC50 = 0.706 ± 0.022 μg/μL; ABTS IC50 = 0.251 ± 0.019 μg/μL), correlated with high phenolic content. Moderate anti-inflammatory activity was confirmed via nitric oxide inhibition. LC-MS profiling indicated diverse metabolites, including phenolic derivatives, aminoglycoside-like compounds, and annotated bioactive molecules. Chromatographic isolation yielded four compounds: 4-(2,3-dihydroxypropoxy)benzoic acid, 4-prenyloxybenzoic acid, and two novel metabolites, xylerithienol and xylerithiether. In silico docking predicted strong interactions of the novel compounds with bacterial targets such as muramyl ligases, DNA gyrase B, and β-ketoacyl-ACP synthase III. Notably, xylerithiether outperformed norfloxacin against DNA gyrase B and fluconazole against sterol 14-α-demethylase. In vitro antibacterial activity was assessed for the purified compounds; all were active, predominantly against Gram-positive bacteria. These finding position X. thienhirunae SWUF17-44.1 as a promising source of bioactive metabolites and potential scaffolds for antimicrobial drug discovery.