Valeria Costantino

Professor of Organic Chemistry

Name Valeria
Surname Costantino
Institution University of Naples – Federico II
Address Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, via Domenico Montesano 49, 80131 Napoli, Italy
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Valeria Costantino


  • Terpioside B, a difucosyl GSL from the marine sponge Terpios sp. is a potent inhibitor of NO release.

    Publication Date: 15/07/2010 on Bioorganic & medicinal chemistry
    by Costantino V, Fattorusso E, Mangoni A, Teta R, Panza E, Ianaro A
    DOI: 10.1016/j.bmc.2010.05.048

    Terpioside B (2a), a unique glycolipid containing two fucose residues in the furanose form in its pentasaccharide chain, was isolated from the marine sponge Terpios sp. Its complete stereostructure was solved by interpretation of mass spectrometric and NMR data along with CD and GG-MS analyses of its degradation products. Terpioside B is a potent inhibitor against LPS-induced NO release, and is considerably more active than simpler glycosphingolipids such as terpioside A and monoglucosylceramide.

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

    Publication Date: 01/11/2009 on Bioorganic & medicinal chemistry
    by Costantino V, Fattorusso E, Mangoni A, Perinu C, Cirino G, De Gruttola L, Roviezzo F
    DOI: 10.1016/j.bmc.2009.09.010

    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.

  • Glycolipids from sponges. 20. J-Coupling analysis for stereochemical assignments in furanosides: structure elucidation of vesparioside B, a glycosphingolipid from the marine sponge Spheciospongia vesparia.

    Publication Date: 15/08/2008 on The Journal of organic chemistry
    by Costantino V, Fattorusso E, Imperatore C, Mangoni A
    DOI: 10.1021/jo800837k

    Reinvestigation of the glycosphingolipid composition of the marine sponge Spheciospongia vesparia revealed the presence of vesparioside B ( 2a), a new furanose-rich hexaglycosylated glycosphingolipid that is the most complex glycosphingolipid isolated from a marine sponge to date. The structure of the new compound was elucidated using extensive 2D NMR studies and chemical degradation. Particularly useful for structure elucidation of vesparioside B was a quantum mechanical computational study, showing that in furanosides a vicinal coupling constant <2.0 Hz (for H-1/H-2 or H-3/H-4) or <3.5 Hz (for H-2/H-3) is a proof of the trans orientation of the relevant protons. This general rule, combined with ROE data, allowed us to elucidate the relative stereochemistry (including anomeric configuration) of the three furanose five-membered rings.

  • Corrugoside, a new immunostimulatory alpha-galactoglycosphingolipid from the marine sponge Axinella corrugata.

    Publication Date: 15/02/2008 on Bioorganic & medicinal chemistry
    by Costantino V, Fattorusso E, Imperatore C, Mangoni A, Freigang S, Teyton L
    DOI: 10.1016/j.bmc.2007.10.098

    Corrugoside (1a), a new immunostimulatory triglycosilated alpha-galactoglycosphingolipid, was isolated from the marine sponge Axinella corrugata, and its structure determined by spectral analysis and chemical degradation. Compound 1a activated murine NKT cells in vitro, with a potency of about 2 logs lower than that of alphaGalCer. Four stereoisomeric glycosphingolipids (2a-2d) were also obtained, beta-glucosylceramides bearing unusual endoperoxide and allylic hydroperoxide functionalities on the sphinganine chain. They were shown to be photooxidation artifacts of the known glycosphingolipids 3, also present in the sponge. A possible role of compound 3 as a singlet oxygen scavenger to protect the organism from oxidative damage is proposed.

  • Synthesis and evaluation of human T cell stimulating activity of an alpha-sulfatide analogue.

    Publication Date: 15/08/2007 on Bioorganic & medicinal chemistry
    by Franchini L, Matto P, Ronchetti F, Panza L, Barbieri L, Costantino V, Mangoni A, Cavallari M, Mori L, De Libero G
    DOI: 10.1016/j.bmc.2007.05.044

    A concise synthesis of alpha-sulfatide 1, an analogue of natural glycolipid antigens with potential anti-tumor activity, was performed. Two different approaches to the alpha-glycosidic bond were explored, resulting in a high yield and excellent stereoselectivity. Compound 1 combines the structural features of sulfated beta-GalCer (sulfatide) and alpha-GalCer, which activate specific T cells. alpha-Sulfatide 1 was stimulatory for CD1d-restricted semi-invariant Natural Killer T (iNKT) cell clones, although less potent than alpha-GalCer, while it was not recognized by CD1a-restricted sulfatide-specific T cells.

  • Glycolipids from sponges. Part 17. Clathrosides and isoclathrosides, unique glycolipids from the Caribbean sponge Agelas clathrodes.

    Publication Date: 01/01/2006 on Journal of natural products
    by Costantino V, Fattorusso E, Imperatore C, Mangoni A
    DOI: 10.1021/np050331v

    Two families of unique glycolipids, clathrosides A-C (2a-4a) and isoclathrosides A-C (5a-7a) were isolated from the Caribbean sponge Agelas clathrodes. Clathrosides and isoclathrosides are glycosides of a very-long-chain alcohol derived from fatty acids, a new class of glycolipids that appears to be characteristic of marine sponges. The six compounds differ in configuration and in the branching of alkyl chains. Stereostructures of the clathrosides were determined by NMR and CD spectroscopy, mass spectrometry, and chemical degradation. Location of the methyl branch on the proper alkyl chain required an exceptional 1-D TOCSY experiment, in which coherence was transferred through as many as 13 vicinal couplings.

  • Damicoside from Axinella damicornis: the influence of a glycosylated galactose 4-OH group on the immunostimulatory activity of alpha-galactoglycosphingolipids.

    Publication Date: 17/11/2005 on Journal of medicinal chemistry
    by Costantino V, D'Esposito M, Fattorusso E, Mangoni A, Basilico N, Parapini S, Taramelli D
    DOI: 10.1021/jm050506y

    Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated galactose 4-OH group. Structure elucidation of damicoside was performed using spectroscopic and chemical methods. When tested in a spleen cell proliferation assay, 3a exhibited a stimulatory activity comparable to that of agelasphin (2), showing that a free galactose 4-OH group is not essential for the immunostimulatory activity of alpha-GalGSLs and providing a further step toward the complete understanding of their structure-activity relationship.

  • Glycolipids from sponges. Part 16.(1) discoside, a rare myo-inositol-containing glycolipid from the caribbean sponge Discodermia dissoluta.

    Publication Date: 01/10/2005 on Journal of natural products
    by Barbieri L, Costantino V, Fattorusso E, Mangoni A
    DOI: 10.1021/np050241q

    Discoside (1a), a glycolipid composed of 4,6-O-diacylated mannose attached to the 2-hydroxyl group of a myo-inositol unit, was isolated as a mixture of homologues from the marine sponge Discodermia dissoluta. The complete stereostructure of this new glycolipid was solved by interpretation of mass spectrometric and NMR data and CD analysis of degradation products.

  • Chemical diversity of bioactive marine natural products: an illustrative case study.

    Publication Date: 01/07/2004 on Current medicinal chemistry
    by Costantino V, Fattorusso E, Menna M, Taglialatela-Scafati O

    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. 13. Clarhamnoside, the first rhamnosylated alpha-galactosylceramide from Agelas clathrodes. Improving spectral strategies for glycoconjugate structure determination.

    Publication Date: 20/02/2004 on The Journal of organic chemistry
    by Costantino V, Fattorusso E, Imperatore C, Mangoni A
    DOI: 10.1021/jo034865h

    Reinvestigation of the glycosphingolipid composition of the marine sponge Agelas clathrodes revealed the presence of a new tetraglycosylated alpha-galactoglycosphingolipid (1a), containing an unusual l-rhamnose unit in the sugar head. The structure of the new compound was elucidated using extensive 2D NMR studies. Because of the strong overlapping of the signals of the sugar protons in the (1)H spectrum, (13)C-coupled and (13)C-decoupled phase-sensitive HMQC spectra were used to study the multiplicity of the overlapping signals. In addition, the absolute configuration of sugars was determined using a simple and efficient, yet underutilized CD method.