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

Abstract

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 tricyclo[4.4.1^1,60^2,7]hendecane 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.

Keywords

Penicillium sp / Cadinane ses-quiterpenoids / Antioxidant activity / Anti-inflammatory / Rearranged carbon skeleton

Funding

This work was supported by Shanghai Municipal Science and Technology Major Project, the National Key Research and Development Program of China (Nos. 2022YFC2804100 and 2020YFA-0509204), the National Natural Science Foundation of China (Nos. 82473795, U24A20808, 82022068, 82173730 and 22137006), and the Innovative Research Team of High-Level Local Universities in Shanghai (SHSMUZDCX20212702).

Declaration of competing interests

These authors have no conflict of interest to declare.

Supporting information

Supplementary data associated with this article can be requested by sending E-mail to the corresponding authors.

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