Bioactive specialized metabolites of Trochila sp., an endophytic fungus of Lilium carniolicum

Bioprospecting of a rice culture of Trochila sp. BGP15P7IS3, an undescribed endophytic fungus from Lilium carniolicum, resulted in isolation and identification of eleven specialized metabolites, of which four pyridone alkaloid derivatives (1, 2, 4, and 5) and a biphenyl derivative (8) were identified as previously undescribed natural products. Moreover, two dibenzofuran derivatives, isousnic acid and usnic acid (9 and 10) with S absolute configuration were reported for the first time from an endophytic fungus. Additionally, the absolute stereochemistry of the previously described compound 7 was determined. The structure of the compounds isolated was established by means of HR-ESI-MS, 1- and 2D NMR, and ECD calculations, as well as utilizing previously published data. All isolates available in sufficient quantities were evaluated for their antimicrobial activity against a plant pathogen, Botrytis cinerea, and four human pathogens, Aspergillus fumigatus, Aspergillus flavus, Candida albicans, and Cryptococcus neoformans, as well as a human sextually transmitted parasite, Trichomonas vaginalis. Compound 3 displayed antifungal activity only against C. neoformans with an MIC value of 12.5 μg/mL, and compound 6 exhibited promising antifungal activity with MIC values of 0.39–3.25 μg/mL against all the aforementioned fungal pathogens, and a concentration-dependent growth inhibitory property against T. vaginalis. Based on the identification of derivatives, a revised biosynthetic pathway for pyridone-type alkaloids was proposed.