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

Publication date: Available online 17 April 2019Source: Chinese Chemical LettersAuthor(s): Fengli Li, Weiguang Sun, Sitian Zhang, Weixi Gao, Shuang Lin, Beiye Yang, Chenwei Chai, Huaqiang Li, Jianping Wang, Zhengxi Hu, Yonghui ZhangAbstractThree 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.Graphical abstractThree new rare cyclopiane diterpenes (1–3) and thirteen known compounds (4–16) were isolated from a sea sediment-derived fungus Penicillium sp. TJ403-2. The absolute structures of 1–3 were confirmed by X-ray crystallography experiment and the anti-inflammatory activity against LPS-in...
Source: Chinese Chemical Letters - Category: Chemistry Source Type: research