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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ftcdlib:oai:escholarship.org/ark:/13030/qt10s7c5mb 2023-05-15T15:11:41+02:00 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 437 - 437 2018-11-08 application/pdf https://escholarship.org/uc/item/10s7c5mb unknown eScholarship, University of California qt10s7c5mb https://escholarship.org/uc/item/10s7c5mb public Marine drugs, vol 16, iss 11 Dendritic Cells CD4-Positive T-Lymphocytes Cells Cultured Animals Humans Geodia Alkaloids Indoles Peptides Cyclic Anti-Inflammatory Agents Interleukin-10 Coculture Techniques Inhibitory Concentration 50 Cell Differentiation Stereoisomerism Iceland Interleukin-12 Subunit p40 Aquatic Organisms 6-bromoindole Geodia barretti T cell differentiation anti-inflammatory activity Physical Chemistry Pharmacology and Pharmaceutical Sciences Medicinal & Biomolecular Chemistry Physical Chemistry (incl. Structural) article 2018 ftcdlib 2021-01-24T17:38:12Z 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. Article in Journal/Newspaper Arctic Iceland University of California: eScholarship Arctic |
institution |
Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Dendritic Cells CD4-Positive T-Lymphocytes Cells Cultured Animals Humans Geodia Alkaloids Indoles Peptides Cyclic Anti-Inflammatory Agents Interleukin-10 Coculture Techniques Inhibitory Concentration 50 Cell Differentiation Stereoisomerism Iceland Interleukin-12 Subunit p40 Aquatic Organisms 6-bromoindole Geodia barretti T cell differentiation anti-inflammatory activity Physical Chemistry Pharmacology and Pharmaceutical Sciences Medicinal & Biomolecular Chemistry Physical Chemistry (incl. Structural) |
spellingShingle |
Dendritic Cells CD4-Positive T-Lymphocytes Cells Cultured Animals Humans Geodia Alkaloids Indoles Peptides Cyclic Anti-Inflammatory Agents Interleukin-10 Coculture Techniques Inhibitory Concentration 50 Cell Differentiation Stereoisomerism Iceland Interleukin-12 Subunit p40 Aquatic Organisms 6-bromoindole Geodia barretti T cell differentiation anti-inflammatory activity Physical Chemistry Pharmacology and Pharmaceutical Sciences Medicinal & Biomolecular Chemistry Physical Chemistry (incl. Structural) 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. |
topic_facet |
Dendritic Cells CD4-Positive T-Lymphocytes Cells Cultured Animals Humans Geodia Alkaloids Indoles Peptides Cyclic Anti-Inflammatory Agents Interleukin-10 Coculture Techniques Inhibitory Concentration 50 Cell Differentiation Stereoisomerism Iceland Interleukin-12 Subunit p40 Aquatic Organisms 6-bromoindole Geodia barretti T cell differentiation anti-inflammatory activity Physical Chemistry Pharmacology and Pharmaceutical Sciences Medicinal & Biomolecular Chemistry Physical Chemistry (incl. Structural) |
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-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. |
format |
Article in Journal/Newspaper |
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 |
title |
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_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_sort |
6-bromoindole derivatives from the icelandic marine sponge geodia barretti: isolation and anti-inflammatory activity. |
publisher |
eScholarship, University of California |
publishDate |
2018 |
url |
https://escholarship.org/uc/item/10s7c5mb |
op_coverage |
437 - 437 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Iceland |
genre_facet |
Arctic Iceland |
op_source |
Marine drugs, vol 16, iss 11 |
op_relation |
qt10s7c5mb https://escholarship.org/uc/item/10s7c5mb |
op_rights |
public |
_version_ |
1766342508847038464 |