Curvulones D–E and Bioactive Cytochalasans from Macrozamia communis-Associated Fungus Penicillium sp. MNP-GP-4

Macrozamia communis (Australian cycad) is the most abundant cycad in Australia, yet its associated fungi lack chemical investigation. As a continuation of our ongoing studies on M. communis-associated fungi, an in-depth chemical exploration of the fermented fungal biomass of Penicillium sp. MNP-GP-4 afforded the identification of two previously undescribed curvularin derivatives, curvulones D (1) and E (2), together with three known metabolites, including curvularin (3) and two cytochalasan derivatives chaetoglobosins E and Fex (4 and 5). Chemical structures of the isolated compounds were elucidated based on comprehensive 1D and 2D NMR spectroscopic analyses and HR-(+)ESI-MS and comparison with the reported literature. All the isolated secondary metabolites were evaluated for their cytotoxic activity against a pancreatic duct adenocarcinoma (PDAC) cell line, where compounds 4 and 5 were the most active with IC50 values of 2.9 and 3.7 µM, respectively.