Eremophilane Sesquiterpenes from the Deep-Sea-Derived Penicillium roseopurpureum 3A00218 and Their Anti-neuroinflammatory Activity

Abstract Eight new eremophilane sesquiterpenes (eremopenicillins A−H, 1−8) were isolated from the deep-sea-derived fungus Penicillium roseopurpureum, along with eight known congeners (9−16). Their structures were elucidated by comprehensive 1D and 2D NMR spectroscopy and HRESIMS analysis, combined with theoretical calculations on the electronic circular dichroism (ECD), NMR chemical shifts, and optical rotations (OR), as well as DP4+ probability analysis. Compounds 1 and 10 showed remarkable anti-neuroinflammatory activity. Quantitative proteomic analysis and molecular dynamics simulations identified NOS2 as their primary molecular target. These two compounds significantly alleviated neurotoxic damage in zebrafish models induced by lipopolysaccharide (LPS), aluminum chloride (AlCl3), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). They not only show promising therapeutic potential for human neurodegenerative diseases, but also represent valuable candidates for the prevention and control of neurotoxic injury caused by environmental pollutants in aquaculture.