Margherita Gavagnin

Structure and cytotoxicity of phidianidines A and B: first finding of 1,2,4-oxadiazole system in a marine natural product.

Two indole alkaloids, phidianidines A (1) and B (2), exhibiting an uncommon 1,2,4-oxadiazole ring linked to the indole system, have been isolated from the marine opisthobranch mollusk Phidiana militaris. The structures of the two metabolites have been elucidated by spectroscopic techniques. Phidianidines exhibit high cytotoxicity against tumor and nontumor mammalian cell lines in in vitro assays.

Factors promoting marine invasions: A chemoecological approach

The Mediterranean Sea is losing its biological distinctiveness, and the same phenomenon is occurring in other seas. It gives urgency to a better understanding of the factors that affect marine biological invasions. A chemoecological approach is proposed here to define biotic conditions that promote biological invasions in terms of enemy escape and resource opportunities. Research has focused on the secondary metabolite composition of three exotic sea slugs found in Greece that have most probably entered the Mediterranean basin by Lessepsian migration, an exchange that contributes significantly to Mediterranean biodiversity. We have found toxic compounds with significant activity as feeding deterrents both in the cephalaspidean Haminoea cyanomarginata and in the nudibranch Melibe viridis. These findings led us to propose aposematism in the former and dietary autonomy in producing defensive metabolites in the latter case, as predisposing factors to the migration. In the third mollusk investigated, the anaspidean Syphonota geographica, the topic of marine invasions has been approached through a study of its feeding biology. The identification of the same compounds from both the viscera of each individual, separately analyzed, and their food, the seagrass Halophila stipulacea, implies a dietary dependency. The survival of S. geographica in the Mediterranean seems to be related to the presence of H. stipulacea. The initial invasion of this exotic pest would seem to have paved the way for the subsequent invasion of a trophic specialist that takes advantage of niche opportunities.

Defensive relationships between Caulerpa prolifera and its shelled sacoglossan predators

Abstract The prey-predator relationship between the green alga Caulerpa prolifera and three shelled sacoglossans, Oxynoe olivaceca, Lobiger serradifalci and Cylindrobulla fragilis , have been investigated in order to clarify the role of the chemical molecules in the defense of both alga and molluscs. Caulerpa prolifera contains as main component, among the secondary metabolites, caulerpenyne (1), a small molecule displaying a sesquiterpenoid skeleton. A defensive role, due to the presence of a protected 1,4-dialdehyde, was previously suggested for caulerpenyne (1). In spite of this protection, three sacoglossans, the infaunal C. fragilis and the epifaunal L. serradifalci and O. olivacea , live closely associated with Caulerpa prolifera . The Thyrrhenian O. olivacea is able to modify the algal metabolite into a couple of more toxic compounds, oxytoxin-1 (2) and -2 (3), characterized by the presence of aldehyde groups. The same defensive strategy is adopted by populations of O. olivacea from Spanish coasts and by populations of C. Fragilis and L. serradifalci from S W Italy. The biotransformation of caulerpenyne (1) leads first to oxytoxin-1 (2), a monoaldehyde, which is compartmentalized into the parapodia of L. serradifalci and into the tail of O. olivacea and then, in O. olivacea and C. fragilis , to oxytoxin-2 (3) which displays the 1,4-conjugated dialdehyde partial moiety, present also in the structure of the potent antifeedant polygodial (4). The presence of the organic molecules has been detected by chemical methods, in particular by NMR (Nuclear Magnetic Resonance) of the extracts of the fresh tissues of the molluscs with deuterated solvents, avoiding any Chromatographie step and chemical treatment.

Oxytoxins, bioactive molecules produced by the marine opisthobranch molluscOxynoe olivacea from a diet-derived precursor

The ethereal extract of the mucous secretion from the opisthobranch molluscOxynoe olivacea was examined and found to contain two novel ichthyotoxic compounds, named oxytoxin 1 and 2 (1, 2). The structures of1 and2 are closely related to the metabolites previously isolated from the algaCaulerpa prolifera. The activity of the most stable compound was studied in order to investigate the possibility, of a further biological role for these metabolites, which represent an uncommon example of bioactive molecules produced in vivo from a dietary precursor.

Rare casbane diterpenoids from the Hainan soft coral Sinularia depressa.

A series of nine casbane diterpenes, compounds 5-13, exhibiting either cis or trans ring junctions were isolated from the Hainan soft coral Sinularia depressa. The structures of this group of compounds, the basic member of which was named depressin (5), were established by detailed spectroscopic analysis. In addition, the absolute configuration of the main metabolite, 10-hydroxydepressin (7), and of its epimer, 1-epi-10-hydroxydepressin (8), was determined by a combination of conformational analysis and the modified Moshers method. A stereochemical relationship between all isolated molecules was investigated by analyzing their circular dichroism profiles. Antiproliferative and antibacterial activities of the depressins were also evaluated.

Verrucosin-A and -B, ichthyotoxic diterpenoic acid glycerides with a new carbon skeleton from the dorid nudibranch Doris verrucosa

Abstract The dorid nudibranch Doris verrucosa contains in its skin extracts two glycerides (2-3)linked to diterpenoid acid residues. The terpenoids show a rearranged tricyclic skeleton. The structures, inferred from spectral and chemical evidence, were unambiguously determined by X-ray diffraction analysis of 3. Both 2 and 3 are highly ichthyotoxic.

Chemical studies of caribbean sacoglossans : Dietary relationships with green algae and ecological implications

Eight sacoglossan species associated with green algae and collected along Caribbean coasts have been chemically investigated, together with their prey. The main secondary metabolites have been identified either by TLC comparison with standard compounds, or by 1H NMR analysis, defining dietary relationships. In addition, two new compounds, ascobullin-A and ascobullin-B, have been found in the sacoglossan Ascobulla ulla and characterized by spectroscopic methods. Finally, the results obtained, together with those already reported for Caribbean sacoglossans, are summarized in a chemoecological scenario, which could be compared with that previously proposed for Mediterranean species.

Glyceryl ester of a new halimane diterpenoic acid from the skin of the antarctic nudibranch Austrodoris kerguelenensis

The monoglyceryl ester (1) of a new halimane diterpenoic acid has been isolated as diacetyl derivative (2) from the mantle tissue of the Antarctic nudibranch Austrodoris kerguelenensis. The structure and the relative stereochemistry have been established by means of spectroscopic and chemical methods and by comparison with model compounds. An analysis of conflicting NMR data reported in literature for molecules related to the diterpenoic part of 1 has also been made.

Austrodoral and austrodoric acid: nor-sesquiterpenes with a new carbon skeleton from the Antarctic nudibranch Austrodoris kerguelenensis

Two unprecedented nor-sesquiterpenes, austrodoral (4) and its oxidised derivative austrodoric acid (5), have been isolated from the skin of the marine dorid Austrodoris kerguelenensis, collected in Antarctica. The structures and the relative stereochemistry were elucidated on the basis of spectroscopic data. A role of stress-metabolites could be suggested for these compounds.

Diterpenes from the Hainan Soft Coral Lobophytum cristatum Tixier-Durivault

Two new prenylgermacrane-type diterpenoids, lobophytumins A and B (1 and 2), two new prenyleudesmane-type diterpenoids, lobophytumins C and D (3 and 4), and two new spatane-type diterpenoids, lobophytumins E and F (5 and 6), were isolated from the Hainan soft coral Lobophytum cristatum Tixier-Durivault. Their structures, including relative configuration, were elucidated by detailed analysis of spectroscopic data and by comparison with related known compounds. In addition, the absolute configuration of lobophytumin C (3) was tentatively assigned by comparing its specific rotation with that of the closely related model compound (-)-β-selinene (8). On the basis of biogenetic considerations, the absolute configurations of lobophytumins A, B, and D-F were also tentatively suggested. This is the first report of spatane-type diterpenoids from a soft coral source. The present work supports Faulkners proposal of prenylgermacrene as the precursor of many diterpenes. In a bioassay, lobophytumins C and D (3 and 4) showed weak in vitro cytotoxicities against the tumor cell lines A-549 and HCT-116.