Further Petroformynes from Both Atlantic and Mediterranean Populations of the Sponge <i>Petrosia </i><i>f</i><i>iciformis</i>

Five novel polyacetylenes (5−9) were isolated from two different populations of the sponge Petrosia ficiformis collected in the Mediterranean Sea and the Atlantic Ocean. Their structures were established by extensive NMR analysis and by comparison with known petroformynes

Novel Inhibitors of Mitochondrial Respiratory Chain: Endoperoxides from the Marine Tunicate <i>Stolonica </i><i>socialis</i>

The Mediterranean tunicate Stolonica socialis contains a new class of powerful cytotoxic acetogenins, generically named stolonoxides. In this paper, which also details the isolation and chemical characterization of a minor component (3a) of the tunicate extract, we report the potent inhibitory activity (IC50 1a and 3a) on mitochondrial electron transfer. The compounds affect specifically the functionality of complex II (succinate:ubiquinone oxidoreductase) and complex III (ubiquinol:cytochrome C oxidoreductase) in mammalian cells, thereby causing a rapid collapse of the whole energetic metabolism. This result, which differs from the properties of similar known products (e.g., 6), reflects the molecular features of stolonoxides

Illudalane Sesquiterpenoids of the Alcyopterosin Series from the Antarctic Marine Soft Coral <i>Alcyonium grandis</i>

Chemical investigation of the lipophilic extract of the Antarctic soft coral Alcyonium grandis led us to the finding of nine unreported sesquiterpenoids, 2−10. These molecules are members of the illudalane class and in particular belong to the group of alcyopterosins, illudalanes isolated from marine organisms. The structures of 2−10 were determined by interpretation of spectroscopic data. Repellency experiments conducted using the omnivorous Antarctic sea star Odontaster validus revealed a strong activity in the lipophilic extract of A. grandis against predation

New Minor Diterpenoid Diacylglycerols from the Skin of the Nudibranch <i>Anisodoris fontaini</i>

The Patagonian dorid nudibranch Anisodoris fontaini contains in its mantle a series of isocopalane diterpenoid diacylglycerols. Five new minor metabolites, anisodorins 1−5 (1−5), along with the already reported 6 and 7, have been isolated and chemically characterized. The structure and the relative stereochemistries have been determined by spectroscopic means, while the absolute stereochemistries for 2−5 are suggested to be the same as for the biogenetically related major compounds 6 and 7. Synthesis of the enantiomer (8) of anisodorin 1 confirmed the proposed structure and absolute stereochemistry

Terpene Biosynthesis in the Nudibranch <i>Doriopsilla </i><i>a</i><i>reolata</i>

Biogenesis of the enantiomeric sesquiterpenes 1 and 5 of the marine nudibranch Doriopsilla areolata was investigated by feeding of [1-13C]glucose, [1,2-13C2]glucose, and [1,2-13C2]acetate. Evidence is presented that supports de novo origin of both compounds via mevalonic acid

Structure and Absolute Stereochemistry of Syphonoside, a Unique Macrocyclic Glycoterpenoid from Marine Organisms

The glycoterpenoid syphonoside (1) is the main secondary metabolite of both the marine mollusk Syphonota geographica and the sea-grass Halophila stipulacea, two Indo-Pacific species migrated to the Mediterranean Sea through the Suez Canal. The structure and the absolute stereochemistry of 1, which displays unique structural features, has been accomplished by using a combination of spectroscopic techniques, degradation reactions, and conformational analysis methods. Compound 1 was able to inhibit high density induced apoptosis in a number of human and murine carcinoma cell lines

Aromatic Cyclic Peroxides and Related Keto-Compounds from the <i>Plakortis</i> sp. Component of a Sponge Consortium

Six unreported aromatic compounds, 1−6, were isolated, along with the known compounds dehydrocurcuphenol and manoalide, from a sample of Plakortis sp., which was the main component of a Pacific sponge consortium. The new molecules were chemically characterized by spectroscopic methods. Compounds 1−4 contain a six-membered cyclic peroxide, whereas 5 and 6 display a terminal methyl ketone. The new metabolites were tested for antifungal and antibacterial properties. Compounds 1 and 4 were weakly active against S. aureus

Sequestered Fulvinol-Related Polyacetylenes in <i>Peltodoris atromaculata</i>

The Mediterranean dorid nudibranch <i>Peltodoris atromaculata</i> that had been collected while feeding on <i>Haliclona fulva</i> was shown to sequester long-chain fulvinol-like polyacetylene metabolites (compounds <b>2</b>–<b>5</b>) from the prey. They were isolated along with previously reported bromorenierins from the diethyl ether extracts of both the mollusk and the sponge. Their structures were elucidated by NMR spectroscopy and tandem FABMS analysis. Compound <b>5</b> exhibited in vitro growth inhibitory effects against the SKMEL-28 melanoma cell line

Minimalist Hybrid Ligand/Receptor-Based Pharmacophore Model for CXCR4 Applied to a Small-Library of Marine Natural Products Led to the Identification of Phidianidine A as a New CXCR4 Ligand Exhibiting Antagonist Activity

Here, we present a minimal hybrid ligand/receptor-based pharmacophore model (PM) for CXCR4, a chemokine receptor deeply involved in several pathologies, such as HIV infection, rheumatoid arthritis, cancer development/progression, and metastasization. This model, considerably simpler than those thus far proposed for this receptor, has been used to search for new CXCR4 inhibitors in a small marine natural product library available at ICB-CNR Institute (Pozzuoli, NA, Italy), since natural products, with their naturally selected chemical and functional diversity, represent a rich source of bioactive scaffolds; computational approaches allow searching for new scaffolds with a minimal waste of possibly precious natural product samples; and our “stripped-down” model substantially increases the probabilities of identifying potential hits even in small-sized libraries. This search, also validated by a systematic virtual screening of the same library, has led to the identification of a new CXCR4 ligand, phidianidine A (PHIA). Docking studies supported PHIA activity and suggested its possible binding modes to CXCR4. Using the CXCR4-expressing/CXCR7-negative GH4C1 cell line we show that PHIA inhibits CXCL12-induced DNA synthesis, cell migration, and ERK1/2 activation. The specificity of these effects was confirmed by the lack of PHIA activity in GH4C1 cells, in which siRNA highly reduces CXCR4 expression and the lack of cytoxicity of PHIA was also verified. Thus, PHIA represents a promising lead for a new family of CXCR4 modulators with wide margins of improvement in potency and specificity offered by the small and very simple underlying PM

Bioactive Terpenes from <i>Spongia officinalis</i>

The terpene metabolite pattern of Mediterranean Spongia officinalis was chemically investigated. This study resulted in the isolation of a series of sesterterpenes and C21 furanoterpenes, according to the literature data on this sponge. Four new oxidized minor metabolites (compounds 1, 2, 3, and 4) were isolated along with six known compounds of the furospongin series (compounds 5–8, 9, and 10) and three scalarane sesterterpenes (compounds 11–13). Interestingly, tetrahydrofurospongin-2 (6) and dihydrofurospongin-2 (7), which were among the main metabolites, induced biofilm formation by Escherichia coli. All compounds isolated were also assayed for antibacterial and antifungal properties