Valeria Costantino

Glycolipids from sponges. IV. Immunomodulating glycosyl ceramides from the marine sponge agelas dispar.

The GSL composition of the marine sponge Agelas dispar was investigated. In addition to four GSLs previously isolated from Agelas clathrodes (2 and 4), Agelas conifera (3), and Agelas longissima (5), the novel triglycosylceramide 1a was isolated as a major component of the GSL mixture. All the isolated GSLs were tested using the MLR assay, and only some of them were shown to be immunoactivating agents, suggesting a possible structure-activity relationship.

Chemical Diversity of Bioactive Marine Natural Products: An Illustrative Case Study

The marine environment contains a number of plants, animals and micro organisms, which, due to the unique adaptations to their habitat, elaborate a wide diversity of natural products with specific bioactivities. These products provide a rich source of chemical diversity that can be used to design and develop new potentially useful therapeutic agents. The huge variety of the structures present in marine organisms has been illustrated through the case study of the sponge Plakortis simplex, whose chemical analysis, started in our laboratories about ten years ago, revealed an incredible variety and abundance of secondary metabolites. The obtained results have been presented with the intention of drawing some conclusions of general relevance. Particularly, the problem of the limited availability of natural compounds for both structural and preliminary pharmacological studies has been discussed, this issue becoming a serious obstacle when the pharmacological research reaches a more advanced stage. Furthermore, the origin of the chemodiversity in Plakortis simplex and, in general, in marine invertebrates has been discussed; in this respect, the possible cooperative role of symbiotic micro-organisms in the biosynthesis of the varied metabolic content typical of these organisms has been considered.

Glycolipids from sponges. VII.1 simplexides, novel immunosuppressive glycolipids from the caribbean sponge Plakortis simplex

The new glycolipids simplexides (1) have been isolated from the marine sponge Plakortis simplex, and their structure determined by spectroscopic data and microgram-scale chemical degradation. Simplexides are composed of long-chain secondary alcohols glycosylated by a disaccharide chain, and represent a new structural kind of glycolipids. Simplexides strongly inhibit proliferation of activated T-cells by a non-cytotoxic mechanism and can be regarded as simple model molecules for designing immunosuppressive drugs.

Okadaic acid in mussels of Adriatic Sea

Abstract The diarrethic shellfish poisoning from mussels, collected in the main producing areas in the seawater off the coast of Emilia-Romagna (Italy), has been investigated. The ether soluble material from hepatopancreas of highly toxic mussels (Mytilus galloprovincialis) was partitioned between n-hexane and methanol-water 9:1. The hydromethanolic phase was successively subjected to repeated chromatographic separations (SiO2, Sephadex LH-20 and reversed-phase HPLC). Following the toxicity of each fraction by mouse lethality test, the presence of okadaic acid has been evidenced through 1H NMR spectroscopy. The investigation of two further toxic fractions is still in progress. The obtained results represent an initial contribution to current Italian legislation and to future health measures to be defined at European Community level.

A mild and easy one-pot procedure for the synthesis of 2-deoxysugars from glycals

Abstract Glycals can be converted into the corresponding 2-deoxysugars in good yields by treatment with N-iodosuccinimide in CH3CN–H2O 95:5 and removal of the iodide group using Na2S2O4 in DMF/H2O at room temperature. This method is easy to apply, sufficiently mild to allow the survival of acid-sensitive groups such as silyl and trityl ethers and less harmful to the environment than metal-based reactions.

New 9,11-secosterols from gorgonia Subergorgia suberosa of the Indian Ocean

Three new 9,11-secosterols, 3 beta,6 alpha,11-trihydroxy-9,11-seco-5 alpha-cholest-7-ene-9-one (1), 24S- (2a), and 24R-methyl-3 beta,6 alpha, 11-trihydroxy-9,11-seco-5 alpha-cholest-7,22E-diene-9-one (2b), were isolated from the Indian Ocean gorgonia, Subergorgia suberosa. Their structures were established by spectroscopic data.

Isolation and assessment of the in vitro anti-tumor activity of smenothiazole A and B, chlorinated thiazole-containing peptide/polyketides from the Caribbean sponge, Smenospongia aurea.

The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism.

Tedanol: a potent anti-inflammatory ent-pimarane diterpene from the Caribbean Sponge Tedania ignis.

Tedanol, a new brominated and sulfated pimarane diterpene was isolated from the Caribbean sponge Tedania ignis. Structure of tedanol was elucidated by mass spectroscopy and extensive NMR studies (including spectral simulation), and its absolute configuration was determined using the Mosher method. Tedanol showed a potent anti-inflammatory activity at 1mg/kg evaluated in vivo in a mouse model of inflammation. After a single intraperitoneal administration, tedanol significantly reduced both the acute and the subchronic phases of carrageenan-induced inflammation. The anti-inflammatory activity was coupled with a strong inhibition of COX-2 expression, inhibition of cellular infiltration measured as mieloperoxidase (MPO) levels, and inhibition of iNOS expression. These features make tedanol a promising template for the development of new anti-inflammatory molecules with low gastrointestinal toxicity.

Smenamides A and B, Chlorinated Peptide/Polyketide Hybrids Containing a Dolapyrrolidinone Unit from the Caribbean Sponge Smenospongia aurea. Evaluation of Their Role as Leads in Antitumor Drug Research

An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS and homo- and heteronuclear 2D NMR experiments. Structures of smenamides suggested that they are products of the cyanobacterial metabolism, and 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea. Smenamides showed potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, which for compound 1 is exerted through a clear pro-apoptotic mechanism. This makes smenamides promising leads for antitumor drug design.

Immunomodulating glycosphingolipids: an efficient synthesis of a 2′-deoxy-α-galactosyl-GSL

Abstract A new and efficient approach to the total synthesis of 2′-deoxy-α-galactosyl glycosphingolipids was accomplished. Commercially available 3,4,6-tri- O -acetylgalactal was used as the chiral starting material for both the sugar and phytosphingosine building blocks required for the synthesis of 1- O -(2-deoxy-α- d -galactopyranosyl)-2-docosanoylamino-1,3,4-octadecanetriol. The key step of the synthetic strategy was the stereoselective α-glycosidation of the azido precursor of sphingosine.