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

https://arctichealth.org/en/permalink/ahliterature295994
Source
Mar Drugs. 2018 Nov 08; 16(11):
Publication Type
Journal Article
Date
Nov-08-2018
Author
Xiaxia Di
Caroline Rouger
Ingibjorg Hardardottir
Jona Freysdottir
Tadeusz F Molinski
Deniz Tasdemir
Sesselja Omarsdottir
Author Affiliation
Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. xid1@hi.is.
Source
Mar Drugs. 2018 Nov 08; 16(11):
Date
Nov-08-2018
Language
English
Publication Type
Journal Article
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-Na-(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-?, 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-? 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.
PubMed ID
30413031 View in PubMed
Less detail

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

https://arctichealth.org/en/permalink/ahliterature298348
Source
Mar Drugs. 2018 Nov 08; 16(11):
Publication Type
Journal Article
Date
Nov-08-2018
Author
Xiaxia Di
Caroline Rouger
Ingibjorg Hardardottir
Jona Freysdottir
Tadeusz F Molinski
Deniz Tasdemir
Sesselja Omarsdottir
Author Affiliation
Faculty of Pharmaceutical Sciences, University of Iceland, Hagi, Hofsvallagata 53, IS-107 Reykjavik, Iceland. xid1@hi.is.
Source
Mar Drugs. 2018 Nov 08; 16(11):
Date
Nov-08-2018
Language
English
Publication Type
Journal Article
Keywords
Alkaloids - chemistry - isolation & purification - pharmacology
Animals
Anti-Inflammatory Agents - chemistry - isolation & purification - pharmacology
Aquatic Organisms
CD4-Positive T-Lymphocytes - drug effects - metabolism
Cell Differentiation - drug effects
Cells, Cultured
Coculture Techniques
Dendritic Cells
Geodia
Humans
Iceland
Indoles - chemistry
Inhibitory Concentration 50
Interleukin-10 - metabolism
Interleukin-12 Subunit p40 - metabolism
Peptides, Cyclic - chemistry - isolation & purification - pharmacology
Stereoisomerism
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-Na-(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-?, 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-? 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.
PubMed ID
30413031 View in PubMed
Less detail