Antibacterial and antifungal screening of natural products sourced from Australian fungi and characterisation of pestalactams D–F

[Display omitted] •Fermentation of Pestalotiopsis sp. yielded 3 caprolactams, pestalactams D–F.•Pestalactams D–F were characterised using NMR, UV and MS data.•A single crystal X-ray structure for 4-O-methylpestalactam A was obtained.•18 fungal natural products were screened for antibacterial and antifungal activity.•Several compounds showed antifungal activity with MIC values⩽50μM. Eighteen natural products sourced from Australian micro- or macro-fungi were screened for antibacterial and antifungal activity. This focused library was comprised of caprolactams, polyamines, quinones, and polyketides, with additional large-scale isolation studies undertaken in order to resupply previously identified compounds. Chemical investigations of the re-fermented culture from the endophytic fungus Pestalotiopsis sp. yielded three caprolactam analogues, pestalactams D–F, along with larger quantities of the known metabolite pestalactam A, which was methylated using diazomethane to yield 4-O-methylpestalactam A. The chemical structures of the previously undescribed fungal metabolites were determined by analysis of 1D/2D NMR and MS data. The structure of 4-O-methylpestalactam A was confirmed following single crystal X-ray diffraction analysis. The antibacterial and antifungal activity of all compounds was assessed, which identified three compounds, (1S,3R)-austrocortirubin, (1S,3S)-austrocortirubin, and 1-deoxyaustrocortirubin with mild activity (100μM) against Gram-positive isolates and one compound, 2-hydroxy-6-methyl-8-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, with activity against Cryptococcus neoformans and Cryptococcus gattii at 50μM.