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Mar Drugs. 2018 Nov 8;16(11). pii: E437. doi: 10.3390/md16110437.

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

Author information

1
Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. xid1@hi.is.
2
Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. xid1@hi.is.
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. caroline.rouger@u-bordeaux.fr.
4
Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. ih@hi.is.
5
Faculty of Medicine, Biomedical Center, University of Iceland, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. ih@hi.is.
6
Department of Immunology and Centre for Rheumatology Research Landspitali-The National University Hospital of Iceland, Hringbraut, IS-101 Reykjavik, Iceland. jonaf@landspitali.is.
7
Faculty of Medicine, Biomedical Center, University of Iceland, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. jonaf@landspitali.is.
8
Department of Chemistry and Biochemistry and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA. tmolinski@ucsd.edu.
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. dtasdemir@geomar.de.
10
Department of Marine Sciences, Faculty of Mathematics and Natural Sciences, Kiel University, Christian-Albrechts-Platz 4, 24118 Kiel, Germany. dtasdemir@geomar.de.
11
Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. sesselo@hi.is.

Abstract

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 (13) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and l-6-bromohypaphorine (7). The chemical structures of compounds 17 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.

KEYWORDS:

6-bromoindole; Geodia barretti; T cell differentiation; anti-inflammatory activity; dendritic cells

PMID:
30413031
PMCID:
PMC6266195
DOI:
10.3390/md16110437
[Indexed for MEDLINE]
Free PMC Article

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