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

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),...

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Autores principales: Di, Xiaxia, Rouger, Caroline, Hardardottir, Ingibjorg, Freysdottir, Jona, Molinski, Tadeusz F., Tasdemir, Deniz, Omarsdottir, Sesselja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266195/
https://www.ncbi.nlm.nih.gov/pubmed/30413031
http://dx.doi.org/10.3390/md16110437
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author Di, Xiaxia
Rouger, Caroline
Hardardottir, Ingibjorg
Freysdottir, Jona
Molinski, Tadeusz F.
Tasdemir, Deniz
Omarsdottir, Sesselja
author_facet Di, Xiaxia
Rouger, Caroline
Hardardottir, Ingibjorg
Freysdottir, Jona
Molinski, Tadeusz F.
Tasdemir, Deniz
Omarsdottir, Sesselja
author_sort Di, Xiaxia
collection PubMed
description 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-N(α)-(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 (IC(50) 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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spelling pubmed-62661952018-12-06 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 F. Tasdemir, Deniz Omarsdottir, Sesselja Mar Drugs Article 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-N(α)-(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 (IC(50) 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. MDPI 2018-11-08 /pmc/articles/PMC6266195/ /pubmed/30413031 http://dx.doi.org/10.3390/md16110437 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di, Xiaxia
Rouger, Caroline
Hardardottir, Ingibjorg
Freysdottir, Jona
Molinski, Tadeusz F.
Tasdemir, Deniz
Omarsdottir, Sesselja
6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity
title 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity
title_full 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity
title_fullStr 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity
title_full_unstemmed 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity
title_short 6-Bromoindole Derivatives from the Icelandic Marine Sponge Geodia barretti: Isolation and Anti-Inflammatory Activity
title_sort 6-bromoindole derivatives from the icelandic marine sponge geodia barretti: isolation and anti-inflammatory activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266195/
https://www.ncbi.nlm.nih.gov/pubmed/30413031
http://dx.doi.org/10.3390/md16110437
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