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 01/2014; 25(1). DOI:10.1002/pca.2468 · 2.45 Impact Factor
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ABSTRACT: A stereoselective synthesis of arylidene N-alkoxydiketopiperazines via oxime-ether formation and intramolecular acylation is described, followed by an acid-catalysed rearrangement-fragmentation to give novel diketopiperazine hemiaminal derivatives with useful bioactivity against certain tumour cell lines.Organic & Biomolecular Chemistry 09/2011; 9(21):7476-81. DOI:10.1039/c1ob05722g · 3.49 Impact Factor
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ABSTRACT: Covering: 2010 and 2011. Previous review: Nat. Prod. Rep., 2010, 27, 1871Natural Product Reports 11/2012; 29(12):1382-1406. DOI:10.1039/C2NP20071F · 10.72 Impact Factor