Indole-diterpenoids, polyketides and oxalicine-related meroterpenoids isolated from a marine-derived Penicillium canescens strain

Marine-derived fungi represent a valuable and under-investigated source of bioactive compounds. Growing in an environment characterized by specific conditions such as high salinity, these organisms produce distinctive chemical entities, including halogenated metabolites that hold great promise for drug discovery. Our previous metabolomics studies showed the presence of halogenated and potentially new compounds in a seawater-derived fungal strain Penicillium canescens MMS194. A comprehensive chemical study conducted on this strain led to the isolation of 15 compounds belonging to three chemical families, indole diterpenoids (1-7), polyketides (8-9) and oxalicine-related meroterpenoids (10-15). Nine compounds (1, 2, 4-6, 8, 10, 12 and 13) were described for the first time, and their structures were determined based on NMR, HRMS, and TDDFT-ECD data. The isolates were evaluated for their cytotoxic, antimicrobial, and antiviral activities. The known chlorinated indole diterpenoid 3 showed the best cytotoxic and antimicrobial activities with IC50 values ranging between 5.0 µM to 34.8 µM. This study suggests the potential of chlorinated fungal metabolites for therapeutic applications, and shows the value of the species P. canescens for the discovery of chemically diverse natural products.