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

• Published in: Marine Drugs
• Main Authors: Di, Xiaxia, Rouger, Caroline, Hardardottir, Ingibjorg, Freysdottir, Jona, Molinski, Tadeusz F, Tasdemir, Deniz, Omarsdottir, Sesselja
• Other Authors: 1 Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. [e-mail]. 2 Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. [e-mail]. 3 GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Marine Natural Products Chemistry Research Unit, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany. [e-mail]. 4 Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. [e-mail]. 5 Faculty of Medicine, Biomedical Center, University of Iceland, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. [e-mail]. 6 Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. [e-mail]. 7 Faculty of Medicine, Biomedical Center, University of Iceland, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. [e-mail]. 8 Department of Chemistry and Biochemistry and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA. [e-mail]. 9 GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Marine Natural Products Chemistry Research Unit, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany. [e-mail]. 10 Department of Marine Sciences, Faculty of Mathematics and Natural Sciences, Kiel University, Christian-Albrechts-Platz 4, 24118 Kiel, Germany. [e-mail]. 11 Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. [e-mail].
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI 2019
• Subjects: 6-bromoindole; Geodia barretti; T cell differentiation; anti-inflammatory activity; dendritic cells; Svampdýr; Lyfjagerð; Lækningar; Geodia; Porifera; Anti-Inflammatory Agents; Arctic; Iceland
• Online Access: http://hdl.handle.net/2336/620778; https://doi.org/10.3390/md16110437

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download 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. University of Iceland Research Fund AVS R&D Fund of Ministry of Fisheries and Agriculture in Iceland Landspitali University Hospital Research Fund Memory Fund of Helga Jonsdottir and Sigurlidi Kristjansson National Institutes of Health