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

Di, Xiaxia, Rouger, Caroline, Hardardottir, Ingibjorg, Freysdottir, Jona , Molinski, Tadeusz, Tasdemir, Deniz and Omarsdottir, Sesselja (2018) 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity. Open Access Marine Drugs, 16 (11). p. 437. DOI 10.3390/md16110437.

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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.

Document Type: Article
Keywords: 6-bromoindole; Geodia barretti; anti-inflammatory activity; dendritic cells; T cell differentiation
Research affiliation: OceanRep > GEOMAR > FB3 Marine Ecology > FB3-MN Marine natural products chemistry
Refereed: Yes
Open Access Journal?: Yes
DOI etc.: 10.3390/md16110437
ISSN: 1660-3397
Date Deposited: 20 Nov 2018 11:57
Last Modified: 01 Feb 2019 15:12
URI: http://oceanrep.geomar.de/id/eprint/44712

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