6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity

• Published in: Marine Drugs
• Main Authors: Di, Xiaxia, Rouger, Caroline, Hardardottir, Ingibjorg, Freysdottir, Jona, Molinski, Tadeusz, Tasdemir, Deniz, Omarsdottir, Sesselja
• Other Authors: Faculty of Pharmaceutical Sciences (UI), Lyfjafræðideild (HÍ), Faculty of Medicine (UI), Læknadeild (HÍ), Lífvísindasetur (HÍ), Biomedical Center (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands (HÍ), University of Iceland (UI)
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2018
• Subjects: 6-bromoindole; Geodia barretti; Anti-inflammatory activity; Dendritic cells; T cell differentiation; Svampdýr; Lyfjagerð; Bólgur; T-frumur; Lyfjafræði; Arctic; Bergen; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/1397; https://doi.org/10.3390/md16110437

Publisher's version (útgefin grein) An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A–C (1–3) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and L-6-bromohypaphorine (7). The chemical structures of compounds 1–7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A (1) was assigned by ECD analysis and Marfey’s method employing the new reagent L-Nα-(1-fluoro-2,4-dinitrophenyl)tryptophanamide (L-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4+ T cells decreased T cell secretion of IFN-γ, indicating a reduction in Th1 differentiation. Although barettin (4) reduced DC secretion of IL-12p40 and IL-10 (IC50 values 11.8 and 21.0 µM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-γ or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type. This research was funded by University of Iceland Research Fund (Doctoral Grant and Project Grant), AVS R&D Fund of Ministry of Fisheries and Agriculture in Iceland, the Landspitali University Hospital Research Fund, and the Memory Fund of Helga Jonsdottir and Sigurlidi Kristjansson. Funding from the National Institutes of Health (to T.F.M, R21 AT009783-01) is acknowledged. Acknowledgments: The authors would like to thank Hans Tore Rapp at the University of Bergen for the identification of animal material, Nathalie Kringlstein for technical assistance, Annaliese Franz at University of California, Davis, for the generous gift of ...