Maria Valeria D’Auria
University of Naples Federico II
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Publication
Featured researches published by Maria Valeria D’Auria.
Journal of Organic Chemistry | 2008
Angela Zampella; Valentina Sepe; Paolo Luciano; Filomena Bellotta; Maria Chiara Monti; Maria Valeria D’Auria; Trine Jepsen; Sylvain Petek; Marie-Thérèse Adeline; Olivier Laprévote; Anne-Marie Aubertin; Cécile Debitus; Christiane Poupat; Alain Ahond
A new anti-HIV cyclodepsipeptide, homophymine A, was isolated from a New Caledonian collection of the marine sponge Homophymia sp. The structure of homophymine A was determined by interpretation of spectroscopic data, acid hydrolysis, and LC-MS analysis. Homophymine A contains 11 amino acid residues and an amide-linked 3-hydroxy-2,4,6-trimethyloctanoic acid moiety. Along with four D-, two L-, and one N-methyl amino acids, it also contains four unusual amino acid residues: (2S,3S,4R)-3,4-diMe-Gln, (2R,3R,4S)-4-amino-2,3-dihydroxy-1,7-heptandioic acid, L-ThrOMe, and (2R,3R,4R)-2-amino-3-hydroxy-4,5-dimethylhexanoic acid. In a cell-based XTT assay, homophymine A exhibited cytoprotective activity against HIV-1 infection with a IC50 of 75 nM.
Organic Letters | 2011
Carmen Festa; Simona De Marino; Valentina Sepe; Maria Valeria D’Auria; Giuseppe Bifulco; Cécile Debitus; Mariarosaria Bucci; Valentina Vellecco; Angela Zampella
Two unprecedented cyclic peptides, solomonamides A and B, were isolated from the marine sponge Theonella swinhoei. The structures were elucidated on the basis of comprehensive 1D and 2D NMR analysis and high-resolution mass spectrometry. A combined approach, involving Marfeys method, QM J based analysis, and DFT J/(13)C calculations, was used for establishing the absolute configuration of the entire molecule. Solomonamide A showed in vivo anti-inflammatory activity.
Journal of Organic Chemistry | 2012
Maria Giovanna Chini; Catharine R. Jones; Angela Zampella; Maria Valeria D’Auria; Barbara Renga; Stefano Fiorucci; Craig P. Butts; Giuseppe Bifulco
Here we report the first application of combined accurate ROE-distance analysis with DFT calculations of NMR chemical shifts to achieve the relative configuration assignment of a marine natural product, conicasterol F, a new polyhydroxylated steroid isolated from the marine sponge Theonella swinhoei. We demonstrate the substantial advantages of this combined approach as a tool for structural studies of natural products, providing a powerful alternative to, or information to underpin, total synthesis when more classical NMR data analysis fails to provide unequivocal results. In this paper, we also describe the isolation and structure elucidation of conicasterol F and its 24-ethyl derivative, theonellasterol I, and their pharmacological evaluation as human nuclear receptor modulators.
Journal of Medicinal Chemistry | 2011
Simona De Marino; Raffaella Ummarino; Maria Valeria D’Auria; Maria Giovanna Chini; Giuseppe Bifulco; Barbara Renga; Claudio D’Amore; Stefano Fiorucci; Cécile Debitus; Angela Zampella
Silica gel column chromatography, followed by HPLC purification on the apolar fraction of the methanol extract of marine sponge Theonella swinhoei, resulted in the isolation of a library of 10 polyhydroxylated steroids which we named theonellasterols B-H (1-7) and conicasterols B-D (8-10). The structures were determined on the basis of extensive spectroscopic data (MS, (1)H and (13)C NMR, COSY, HSQC, HMBC, and ROESY) analysis, and the putative binding mode to nuclear receptors (NRs) has been obtained through docking calculations. Pharmacological and structure-activity relationship analysis demonstrate that these natural polyhydroxylated steroids are potent ligands of human nuclear pregnane receptor (PXR) and modulator of farnesoid-X-receptor (FXR). In addition, the molecular characterization of theonellasterol G allowed the identification of the first FXR modulator and PXR ligand so far identified. Exposure of liver cells to this agent resulted in potent induction of PXR-regulated genes and modulation of FXR-regulated genes, highlighting its pharmacological potential in the treatment of liver disorders.
Journal of Medicinal Chemistry | 2011
Carmen Festa; Simona De Marino; Maria Valeria D’Auria; Giuseppe Bifulco; Barbara Renga; Stefano Fiorucci; Sylvain Petek; Angela Zampella
The finding of new PXR modulators as potential leads for treatment of human disorders characterized by dysregulation of innate immunity and with inflammation is of wide interest. In this paper, we report the identification of the first example of natural marine PXR agonists, solomonsterols A and B, from a Theonella swinhoei sponge. The structures were determined by interpretation of NMR and ESIMS data, and the putative binding mode to PXR has been obtained through docking calculations.
Journal of Medicinal Chemistry | 2013
Francesco Saverio Di Leva; Carmen Festa; Claudio D’Amore; Simona De Marino; Barbara Renga; Maria Valeria D’Auria; Ettore Novellino; Vittorio Limongelli; Angela Zampella; Stefano Fiorucci
Here, we report suvanine, a marine sponge sesterterpene, as an antagonist of the mammalian bile acid sensor farnesoid-X-receptor (FXR). Using suvanine as a template, we shed light on the molecular bases of FXR antagonism, identifying the essential conformational changes responsible for the transition from the agonist to the antagonist form. Molecular characterization of the nuclear corepressor NCoR and coactivator Src-1 revealed that receptor conformational changes are associated with a specific dynamic of recruitment of these cofactors to the promoter of OSTα, a FXR regulated gene. Using suvanine as a novel hit, a library of semisynthetic derivatives has been designed and prepared, leading to pharmacological profiles ranging from agonism to antagonism toward FXR. Deep pharmacological evaluation demonstrated that derivative 19 represents a new chemotype of FXR modulator, whereas alcohol 6, with a simplified molecular scaffold, exhibits excellent antagonistic activity.
Steroids | 2012
Simona De Marino; Raffaella Ummarino; Maria Valeria D’Auria; Maria Giovanna Chini; Giuseppe Bifulco; Claudio D’Amore; Barbara Renga; Andrea Mencarelli; Sylvain Petek; Stefano Fiorucci; Angela Zampella
We report the isolation and the structural elucidation of a family of polyhydroxylated steroids from the marine sponge Theonella swinhoei. Decodification of interactions of these family with nuclear receptors shows that these steroids are potent agonists of human pregnane-X-receptor (PXR) and antagonists of human farnesoid-X-receptor (FXR) with the putative binding mode to nuclear receptors (NRs) obtained through docking experiments. By using monocytes isolated from transgenic mice harboring hPXR, we demonstrated that swinhosterol B counter-regulates induction of pro-inflammatory cytokines in a PXR-dependent manner. Exposure of CD4(+) T cells to swinhosterol B upregulates the expression of IL-10 causing a shift toward a T cells regulatory phenotype in a PXR dependent manner. These results pave the way to development of a dual PXR agonist/FXR antagonist with a robust immunomodulatory activity and endowed with the ability to modulate the expression of bile acid-regulated genes in the liver.
Trends in Pharmacological Sciences | 2012
Stefano Fiorucci; Eleonora Distrutti; Giuseppe Bifulco; Maria Valeria D’Auria; Angela Zampella
Nuclear receptors (NRs) are a large family of evolutionarily conserved and ligand-regulated transcription factors. The farnesoid X receptor (FXR) and the pregnane X receptor (PXR) are two bile-acid-activated receptors highly expressed in enterohepatic tissues essential for bile acids and xenobiotic metabolism. More than 1600 new steroidal structures have been isolated from marine organisms. Chemical, structural, and pharmacological characterization of sponge steroid libraries has allowed the identification of steroids that regulate FXR and PXR: selective FXR antagonists, FXR modulators, FXR antagonists endowed with PXR agonism, and selective PXR agonists. Selective FXR antagonists (theonellasterol) have proven effective in protecting against liver injury in models of cholestasis. Selective PXR agonists (natural and synthetic solomonsterols) have been effective in reducing nuclear factor (NF)-κB activity and intestinal inflammation. Identification of marine steroids endowed with dual FXR and PXR agonism-antagonism probably reflects the common identity of the unique ancestral precursor of these NRs. These findings pave the way to the development of novel FXR and PXR agonists and antagonists to target human diseases.
Journal of Medicinal Chemistry | 2012
Carmen Festa; Gianluigi Lauro; Simona De Marino; Maria Valeria D’Auria; Maria Chiara Monti; Agostino Casapullo; Claudio D’Amore; Barbara Renga; Andrea Mencarelli; Sylvain Petek; Giuseppe Bifulco; Stefano Fiorucci; Angela Zampella
In this paper we report the isolation and the molecular characterization of a new class of PPARγ ligands from the marine environment. Biochemical characterization of a library of 13 oxygenated polyketides isolated from the marine sponge Plakinastrella mamillaris allowed the discovery of gracilioether B and plakilactone C as selective PPARγ ligands in transactivation assays. Both agents covalently bind to the PPARγ ligand binding domain through a Michael addition reaction involving a protein cysteine residue and the α,β-unsaturated ketone in their side chains. Additionally, gracilioether C is a noncovalent agonist for PPARγ, and methyl esters 1 and 2 are noncovalent antagonists. Structural requirements for the interaction of these agents within the PPARγ ligand binding domain were obtained by docking analysis. Gracilioether B and plakilactone C regulate the expression of PPARγ-dependent genes in the liver and inhibit the generation of inflammatory mediators by macrophages.
Tetrahedron Letters | 2000
Clelia Giannini; Cécile Debitus; Inmaculada Posadas; Miguel Payá; Maria Valeria D’Auria
Abstract A new bioactive sesquiterpenoid, named dysidotronic acid 1 , with a rearranged drimane skeleton has been isolated from the sponge Dysidea sp. from Vanuatu islands, along with bolinaquinone 2 . The chemical structure of 1 was determined on the basis of spectroscopic data. Dysidotronic acid significantly inhibited human synovial phospholipase A 2 (PLA 2 ) at 10 μM, with an IC 50 value of 2.6 μM and a higher selectivity and potency towards this enzyme than the reference inhibitor manoalide.