Antibacterial Secondary Metabolites from an Endophytic Fungus, <i>Eupenicillium</i> sp. LG41

Two new compounds containing the decalin moiety, eupenicinicols A and B (1 and 2), two new sirenin derivatives, eupenicisirenins A and B (3 and 4), and four known compounds, (2S)-butylitaconic acid (5), (2S)-hexylitaconic acid (6), xanthomegnin (7), and viridicatumtoxin (8), were isolated from an endophytic fungus, Eupenicillium sp. LG41, harbored in the roots of the Chinese medicinal plant Xanthium sibiricum. Their structures were confirmed through combined spectroscopic analysis (NMR and HRMS(n)), and their absolute configurations were deduced by ECD calculations or optical rotation data. Since the endophytic fungus was isolated from the roots, the antibacterial efficacies of the compounds 1-6 were investigated against Bacillus subtilis and Acinetobacter sp. BD4, which typically inhabit soil, as well as the clinically important Staphylococcus aureus and Escherichia coli. (2S)-Butylitaconic acid (5) and (2S)-hexylitaconic acid (6) exhibited pronounced efficacy against Acinetobacter sp., corroborating the notion that root-endophytes provide chemical defense to the host plants. Compound 2 was highly active against the clinically relevant S. aureus. By comparing 1 with 2, it was revealed that altering the substitution at C-11 could drastically increase the antibacterial efficacy of 1. Our study reveals plausible ecological roles of the endophyte and its potential pharmaceutical use as a source of antibacterial compounds.