Two brominated cyclic dipeptides released by the coldwater marine sponge Geodia barretti act in synergy as chemical defense.
ABSTRACT The current work shows that two structurally similar cyclodipeptides, barettin (1) and 8,9-dihydrobarettin (2), produced by the coldwater marine sponge Geodia barretti Bowerbank act in synergy to deter larvae of surface settlers and may also be involved in defense against grazers. Previously, 1 and 2 were demonstrated to bind specifically to serotonergic 5-HT receptors. It may be suggested that chemical defense in G. barretti involves a synergistic action where one of the molecular targets is a 5-HT receptor. A mixture of 1 and 2 lowered the EC(50) of larval settlement as compared to the calculated theoretical additive effect of the two compounds. Moreover, an in situ sampling at 120 m depth using a remotely operated vehicle revealed that the sponge releases these two compounds to the ambient water. Thus, it is suggested that the synergistic action of 1 and 2 may benefit the sponge by reducing the expenditure of continuous production and release of its chemical defense substances. Furthermore, a synergistic action between structurally closely related compounds produced by the same bioenzymatic machinery ought to be the most energy effective for the organism and, thus, is more common than synergy between structurally indistinct compounds.
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ABSTRACT: Identifying bioactive molecules from complex biomasses requires careful selection and execution of relevant bioassays in the various stages of the discovery process of potential leads and targets. The aim of this review is to share our long-term experience in bioassay-guided isolation, and mechanistic studies, of bioactive compounds from different organisms in nature with emphasis on anti-inflammatory and antimicrobial activity. In the search for anti-inflammatory activity, in vivo and in vitro model combinations with enzymes and cells involved in the inflammatory process have been used, such as cyclooxygenases, human neutrophils and human cancer cell lines. Methods concerning adsorption and perforation of bacteria, fungi, human cells and model membranes, have been developed and optimised, with emphasis on antimicrobial peptides and their interaction with the membrane target, in particular their ability to distinguish host from pathogen. A long-term research has provided experience of selection and combination of bioassay models, which has led to an increased understanding of ethnopharmacological and ecological observations, together with in-depth knowledge of mode of action of isolated compounds. A more multidisciplinary approach and a higher degree of fundamental research in development of bioassays are often necessary to identify and to fully understand the mode of action of bioactive molecules with novel structure-activity relationships from natural sources. Copyright © 2013 John Wiley & Sons, Ltd.Phytochemical Analysis 09/2013; · 2.48 Impact Factor
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ABSTRACT: Covering: 1995 to early 2013This review covers the isolation, chemical structure, biological activity, structure activity relationships including synthesis of chemical probes, and pharmacological characterization of neuroactive marine natural products; 302 references are cited.Natural Product Reports 01/2014; 31(2):273-309. · 10.72 Impact Factor
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ABSTRACT: Geodia species north of 60°N in the Atlantic appeared in the literature for the first time when Bowerbank described Geodia barretti and G. macandrewii in 1858 from western Norway. Since then, a number of species have been based on material from various parts of the region: G. simplex, Isops phlegraei, I. pallida, I. sphaeroides, Synops pyriformis, G. parva, G. normani, G. atlantica, Sidonops mesotriaena (now called G. hentscheli), and G. simplicissima. In addition to these 12 nominal species, four species described from elsewhere are claimed to have been identified in material from the northeast Atlantic, namely G. nodastrella and G. cydonium (and its synonyms Cydonium muelleri and Geodia gigas). In this paper, we revise the boreo‐arctic Geodia species using morphological, molecular, and biogeographical data. We notably compare northwest and northeast Atlantic specimens. Biological data (reproduction, biochemistry, microbiology, epibionts) for each species are also reviewed. Our results show that there are six valid species of boreo‐arctic Atlantic Geodia while other names are synonyms or mis‐identifications. Geodia barretti, G. atlantica, G. macandrewii, and G. hentscheli are well established and widely distributed. The same goes for Geodia phlegraei, but this species shows a striking geographical and bathymetric variation, which led us to recognize two species, G. phlegraei and G. parva (here resurrected). Some Geodia are arctic species (G. hentscheli, G. parva), while others are typically boreal (G. atlantica, G. barretti, G. phlegraei, G. macandrewii). No morphological differences were found between specimens from the northeast and northwest Atlantic, except for G. parva. The Folmer cytochrome oxidase subunit I (COI) fragment is unique for every species and invariable over their whole distribution range, except for G. barretti which had two haplotypes. 18S is unique for four species but cannot discriminate G. phlegraei and G. parva. Two keys to the boreo‐arctic Geodia are included, one based on external morphology, the other based on spicule morphology. © 2013 The Linnean Society of LondonZoological Journal of the Linnean Society 10/2013; 169(2). · 2.66 Impact Factor