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Antifouling activity of a dibrominated cyclopeptide from the marine sponge Geodia barretti
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
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2008 (English)In: Journal of natural products (Print), ISSN 0163-3864, E-ISSN 1520-6025, Vol. 71, no 3, 330-333 p.Article in journal (Refereed) Published
Abstract [en]

Many sessile suspension-feeding marine organisms rely on chemical defense to keep their surfaces free from fouling organisms. The brominated cyclopeptides barettin (cyclo[(6-bromo-8-entryptophan)arginine]) (1) and 8,9-dihydrobarettin (cyclo[(6-bromotryptophan)arginine]) (2) from the cold-water sponge Geodia barretti have previously displayed settlement inhibition of barnacle larvae in a dose-dependent manner. In this paper, we describe a novel dibrominated cyclopeptide, bromobenzisoxazolone barettin (cyclo[(6-bromo-8-(6-bromobenzioxazol-3(1H)-one)-8-hydroxy)tryptophan)]arginine) (3), which we have isolated from G. barretti and which displays settlement inhibition of barnacle larvae (Balanus improvisus) with an EC50 value of 15 nM. The chemical structure was determined using MS and 2D-NMR.

Place, publisher, year, edition, pages
2008. Vol. 71, no 3, 330-333 p.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-96228DOI: 10.1021/np0705209ISI: 000254544900007PubMedID: 18271554OAI: oai:DiVA.org:uu-96228DiVA: diva2:170731
Available from: 2007-09-27 Created: 2007-09-27 Last updated: 2012-01-23Bibliographically approved
In thesis
1. Bioactive Compounds in the Chemical Defence of Marine Sponges: Structure-Activity Relationships and Pharmacological Targets
Open this publication in new window or tab >>Bioactive Compounds in the Chemical Defence of Marine Sponges: Structure-Activity Relationships and Pharmacological Targets
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Marine invertebrates, in particular sponges, represent a source of a wide range of secondary metabolites, many of which have been attributed various defensive capabilities against environmental stress factors. In this thesis sponge-derived low-molecular peptide-like compounds and associated analogs are investigated for bioactivity and pharmacological targets.

The compound bromobenzisoxazolone barettin (cyclo[(6-bromo-8-(6-bromo-benzioxazol -3(1H)-one)-8-hydroxy)tryptophan)]arginine) was isolated from the sponge Geodia barretti and its ability to inhibit larval settlement of the barnacle Balanus improvisus was determined. With an EC50 value of 15 nM, this compound’s antifouling effect was higher than those of the previously reported brominated dipeptides from Geodia barretti, i.e., barettin and 8,9-dihydrobarettin; moreover, this antifouling effect was demonstrated to be reversible. However, the compound lacked affinity for 5-HT1-7 receptors, whereas barettin possessed specific affinity to 5-HT2A, 5-HT2C and 5-HT4, while 8,9-dihydrobarettin interacted with 5-HT4. In an attempt to evaluate structure-activity relationships synthesized analogs with barettin and dipodazine scaffolds were investigated for antifouling activity. The analog benso[g]dipodazine, with an EC50 value of 34 nM, displayed the highest settlement inhibition.

The studies of the structure-activity relationships of sponge-derived compounds were extended to cover analogs of agelasines and agelasimines originally isolated from sponges of the genus Agelas. Synthesized (+)-agelasine D and two structurally close analogs were investigated for cytotoxic and antibacterial activity. The profound cytotoxicity and broad spectrum antibacterial activity found prompted a further investigation of structure-activity relationships in 42 agelasine and agelasimine analogs and several characteristics that increased bioactivity were identified.

In conclusion this work has produced new results regarding the potent bioactivity of compounds derived from the sponges Geodia barretti and Agelas spp. and increased SAR knowledge of the fouling inhibition, cytotoxicity and antimicrobial activity of these compounds.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 63
Keyword
Pharmacognosy, 5-hydroxytryptamine, agelasine, agelasimine, antibacterial, antifouling, barettin, bromobenzisoxazolone barettin, cytotoxic, marine, secondary metabolite, sponge, Farmakognosi, Agelas, Geodia barretti
Identifiers
urn:nbn:se:uu:diva-8218 (URN)978-91-554-6971-9 (ISBN)
Public defence
2007-10-19, B7:113a, BMC, BMC, Uppsala, 13:15
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Supervisors
Available from: 2007-09-27 Created: 2007-09-27 Last updated: 2011-06-16Bibliographically approved

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