Copper ion-based chemical elicitation induces production of new benzofurans in Anthostomella brabeji, an endophytic fungus of Paepalanthus planifolius

The present work reports the effects of chemical elicitors and epigenetic modifiers on the production and diversification of secondary metabolites produced by Anthostomella brabeji - an endophytic fungus isolated from Paepalanthus planifolius (Eriocaulaceae). The fungus was cultivated under four different small-scale culture conditions in potato dextrose broth (PDB): PDB (control), PDB + Mg+2, PDB + Cu+2 and PDB + 5-AZA (5-azacytidine). The incorporation of Cu+2 into PDB medium yielded the most promising results as the most significant differences in the metabolic profile of A. brabeji were observed under this condition. The chemical analysis of the PDB + Cu+2 extract resulted in the isolation of seven metabolites, including three new benzofuran derivatives (2, 4 and 6) and four known compounds (1, 3, 5 and 7). The metabolites were tested using the Gram-positive bacterium Staphylococcus aureus, Gram-negative bacteria Salmonella sp. and Escherichia coli, and six yeasts of Candida albicans and non-albicans. The EtOAc extract (PDB + Cu+2), and compounds 1, 2 and 7 exhibited relevant antifungal activity against Candida spp., with minimum inhibitory concentration ranging from 62.5 to 500.0 μg/mL.