Integrated molecular networking-guided discovery of antimicrobial secondary metabolites from Thyronectria pinicola

Abstract

Using an LC-MS/MS-based molecular networking-guided approach, three previously undescribed chlorinated resorcylic acid lactone derivatives (5–7), two new cleistanthane-type diterpenoids (11–12) and a new dimeric derivative (13), together with seven known metabolites, were isolated from a cereal culture of Thyronectria pinicola (Ascomycota: Hypocreales). T. pinicola was isolated from a fruiting body of the devils'tooth mushroom, Hydnellum peckii (Basidiomycota, Thelephorales). The structures of the isolated compounds were elucidated using 1D and 2D NMR spectroscopy and HRMS, and their absolute configurations were established by electronic circular dichroism (ECD) calculations or X-ray crystallography. All metabolites were evaluated for their bioactivities against three major human fungal pathogens, Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. The results indicated that compound 1 was the most active substance, with MIC values ranging from 1.5 to 50 µg mL−1 against all three species. In contrast, compounds 5 and 10 displayed only moderate activity against A. fumigatus and C. neoformans.