Penicipenoids A−G, Antioxidant and Anti-inflammatory Cadinane Sesquiterpenoids with Rearranged Carbon Skeletons from the Marine Sponge Symbiotic Penicillium sp. 5975

Seven new sesquiterpenes, penicipenoids A−G (1−7), were isolated from the rice fermentation of a strain of marine sponge symbiotic fungus Penicillium sp. 5975, along with ten known analogues (8−17). The chemical structures of new compounds were determined by HRMS and NMR data analyses coupled with single-crystal X-ray diffraction and ECD calculations. Penicipenoid A (1) possessed an unprecedented sesquiterpene carbon skeleton with a tricyclo4.4.1^1,60^2,7hendecane core. Penicipenoid D (4) featured an unusual furan substructure in the cadinane family sesquiterpenoids, while penicipenoid F (6) was a rare norsesquiterpene derivative with a loss of carbon at C-7 position. The in vivo antioxidant and anti-inflammatory activities of these isolates were investigated using transgenic fluorescent zebrafish models. Penicipenoids A−C (1−3) showed antioxidant activity in metronidazole (MTZ)-treatment transgenic zebrafish embryos, and penicipenoid E (5) exhibited potent anti-inflammatory activity in CuSO₄-induced transgenic fluorescent zebrafish embryos.