Title: | 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity |
Author: |
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Date: | 2018-11-08 |
Language: | English |
Scope: | 437 |
University/Institute: | Háskóli Íslands (HÍ) University of Iceland (UI) |
School: | Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) |
Department: | Faculty of Pharmaceutical Sciences (UI) Lyfjafræðideild (HÍ) Faculty of Medicine (UI) Læknadeild (HÍ) Lífvísindasetur (HÍ) Biomedical Center (UI) |
Series: | Marine Drugs;16(11) |
ISSN: | 1660-3397 |
DOI: | 10.3390/md16110437 |
Subject: | 6-bromoindole; Geodia barretti; Anti-inflammatory activity; Dendritic cells; T cell differentiation; Svampdýr; Lyfjagerð; Bólgur; T-frumur; Lyfjafræði |
URI: | https://hdl.handle.net/20.500.11815/1397 |
Citation:Di, X.; Rouger, C.; Hardardottir, I.; Freysdottir, J.; Molinski, T.F.; Tasdemir, D.; Omarsdottir, S. 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity. Mar. Drugs 2018, 16, 437.
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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 (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.
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Description:Publisher's version (útgefin grein)
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Rights:This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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