dc.contributor |
Háskóli Íslands (HÍ) |
dc.contributor |
University of Iceland (UI) |
dc.contributor.author |
Di, Xiaxia |
dc.contributor.author |
Rouger, Caroline |
dc.contributor.author |
Hardardottir, Ingibjorg |
dc.contributor.author |
Freysdottir, Jona |
dc.contributor.author |
Molinski, Tadeusz |
dc.contributor.author |
Tasdemir, Deniz |
dc.contributor.author |
Omarsdottir, Sesselja |
dc.date.accessioned |
2019-12-16T14:38:52Z |
dc.date.available |
2019-12-16T14:38:52Z |
dc.date.issued |
2018-11-08 |
dc.identifier.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. |
dc.identifier.issn |
1660-3397 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/1397 |
dc.description |
Publisher's version (útgefin grein) |
dc.description.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. |
dc.description.sponsorship |
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 8a, Sigridur Jonsdottir at University of Iceland for running NMR
spectra on a Bruker AM-400 spectrometer, Finnur Freyr Eiriksson and Margret Thorsteinsdottir for running
UPLC-qTOF-MS and Kare Telnes for giving the permission to use the sponge picture in the Graphical abstract. |
dc.format.extent |
437 |
dc.language.iso |
en |
dc.publisher |
MDPI AG |
dc.relation.ispartofseries |
Marine Drugs;16(11) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
6-bromoindole |
dc.subject |
Geodia barretti |
dc.subject |
Anti-inflammatory activity |
dc.subject |
Dendritic cells |
dc.subject |
T cell differentiation |
dc.subject |
Svampdýr |
dc.subject |
Lyfjagerð |
dc.subject |
Bólgur |
dc.subject |
T-frumur |
dc.subject |
Lyfjafræði |
dc.title |
6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
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 |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
Marine Drugs |
dc.identifier.doi |
10.3390/md16110437 |
dc.relation.url |
http://www.mdpi.com/1660-3397/16/11/437/pdf |
dc.contributor.department |
Faculty of Pharmaceutical Sciences (UI) |
dc.contributor.department |
Lyfjafræðideild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Lífvísindasetur (HÍ) |
dc.contributor.department |
Biomedical Center (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |