New cyclopiane diterpenes with anti-inflammatory activity from the sea sediment-derived fungus Penicillium sp. TJ403-2

Three new rare cyclopiane diterpenes (1-3), together with thirteen known compounds (4-16), were isolated and identified from a sea sediment-derived fungus Penicillium sp. TJ403-2. The planar and relative structures of compounds 1-3 were elucidated by HRESIMS, one- and two-dimensional NMR analyses, and their absolute configurations were further established by X-ray crystallography experiment. Compounds 1-3 were evaluated for the anti-inflammatory activity against LPS-induced NO production, and compound 1 showed notable inhibitory potency with an IC₅₀ value of 2.19±0.25 μmol/L, which was three fold lower than the positive control indomethacin (IC₅₀=8.76±0.92 μmol/L). Further Western blot and immunofluorescence experiments demonstrated its mechanism of action to be that 1 inhibited the NF-ΚB-activated pathway, highlighting it as a promising starting point for the development of new anti-inflammatory agents.