Penicipenoids A−G, antioxidant and anti-inflammatory cadinane sesquiterpenoids with rearranged carbon skeletons from the marine sponge symbiotic Penicillium sp. 5975

Seven new sesquiterpenes, named penicipenoids A−G (1−7), were isolated from rice-based fermentation cultures of the marine sponge-derived fungus Penicillium sp. 5975, together with ten known analogues (8−17). Their structures were elucidated using high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy, supported by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations. Penicipenoid A (1) features an unprecedented sesquiterpene scaffold characterized by a tricyclo4.4.1^1,60^2,7hendecane core. Penicipenoid D (4) contains an unusual furan substructure within the cadinane-type sesquiterpenoid class, while penicipenoid F (6) represents a rare norsesquiterpene derivative lacking the carbon atom at the C-7 position. The in vivo anti-oxidant and anti-inflammatory effects of these compounds were evaluated using transgenic fluorescent zebrafish models. Penicipenoids A−C (1−3) exhibited anti-oxidant activity in metronidazole (MTZ)-treated transgenic zebrafish embryos, whereas penicipenoid E (5) demonstrated potent anti-inflammatory activity in CuSO₄-induced transgenic fluorescent zebrafish embryos.