Solomonsterols A and B from Theonella swinhoei. The first example of C-24 and C-23 sulfated sterols from a marine source endowed with a PXR agonistic activity.

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.

[1]  F. Koehn,et al.  Weinbersterol Disulfates A and B, Antiviral Steroid Sulfates from the Sponge Petrosia weinbergi , 1991 .

[2]  Y. Itoh,et al.  Isolation and structure elucidation of two phosphorylated sterol sulfates, MT1-MMP inhibitors from a marine sponge Cribrochalina sp.: revision of the structures of haplosamates A and B , 2001 .

[3]  V. Sepe,et al.  Perthamides C and D, two new potent anti-inflammatory cyclopeptides from a Solomon Lithistid sponge Theonella swinhoei , 2009 .

[4]  J. Mcmahon,et al.  HIV-inhibitory natural products. 11. Comparative studies of sulfated sterols from marine invertebrates. , 1994, Journal of medicinal chemistry.

[5]  F. Koehn,et al.  New antiviral sterol disulfate ortho esters from the marine sponge Petrosia weinbergi , 1991 .

[6]  Jongki Hong,et al.  Bile acid derivatives from a sponge-associated bacterium Psychrobacter sp. , 2009, Archives of pharmacal research.

[7]  G. Bifulco,et al.  Novel HIV-inhibitory halistanol sulfates F-H from a marine sponge, Pseudoaxinissa digitata. , 1994, Journal of natural products.

[8]  F. Koehn,et al.  Weinbersterol disulfates A and B, antiviral steroid sulfates from the sponge petrosia weinbergi , 1991 .

[9]  V. Stonik,et al.  New polar steroids from the sponges Trachyopsis halichondroides and Cymbastela coralliophila , 1995, Steroids.

[10]  R. Riccio,et al.  Polyoxygenated Steroids of Marine Origin , 1993 .

[11]  Sean Ekins,et al.  Challenges Predicting Ligand-Receptor Interactions of Promiscuous Proteins: The Nuclear Receptor PXR , 2009, PLoS Comput. Biol..

[12]  J. Thompson,et al.  Biologically-active sterol sulfates from the marine spongeToxadocia zumi , 1983, Experientia.

[13]  M. Kelly-Borges,et al.  Ophirapstanol trisulfate, a new biologically active steroid sulfate from the deep water marine sponge Topsentia ophiraphidites. , 1994, Journal of natural products.

[14]  E. Distrutti,et al.  Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells. , 2010, Biochemical pharmacology.

[15]  K. Morimura,et al.  Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-κB target gene expression , 2007 .

[16]  Fernando Ontiveros,et al.  The sterile inflammatory response. , 2010, Annual review of immunology.

[17]  J. Idle,et al.  Rifaximin Is a Gut-Specific Human Pregnane X Receptor Activator , 2007, Journal of Pharmacology and Experimental Therapeutics.

[18]  S. Matsunaga,et al.  Bioactive marine metabolites II. Halistanol sulfate, an antimicrobial novel steroid sulfate from the marine sponge halichondria cf. moorei bergquist , 1981 .

[19]  M. Boyd,et al.  Ibisterol sulfate, a novel HIV-inhibitory sulfated sterol from the deep water sponge Topsentia sp. , 1993 .

[20]  D. Ferreira,et al.  Reversal of fluconazole resistance by sulfated sterols from the marine sponge Topsentia sp. , 2009, Journal of natural products.

[21]  M. K. Harper,et al.  Spheciosterol Sulfates, PKCζ Inhibitors from a Philippine Sponge Spheciospongia sp. , 2008, Journal of natural products.

[22]  V. Stonik,et al.  Topsentiasterol sulfates with novel iodinated and chlorinated side chains from the marine sponge Topsentia sp. , 2008 .

[23]  B. David,et al.  Isolation and absolute configuration of new bioactive marine steroids from Euryspongia n. sp. , 2005, Steroids.

[24]  H. Guzman,et al.  Antiplasmodial metabolites isolated from the marine octocoral Muricea austera. , 2006, Journal of natural products.

[25]  A. Hizi,et al.  Clathsterol, a novel anti-HIV-1 RT sulfated sterol from the sponge Clathria species. , 2001, Journal of natural products.

[26]  T. Furukawa,et al.  Lembehsterols A and B, Novel Sulfated Sterols Inhibiting Thymidine Phosphorylase, from the Marine Sponge Petrosia strongylata. , 2002 .

[27]  P. Di Meglio,et al.  Polychlorinated androstanes from the burrowing sponge Cliona nigricans. , 2004, Organic letters.

[28]  R. Riccio,et al.  Novel marine steroid sulfates from Pacific ophiuroids , 1987 .

[29]  P. Crews,et al.  Geodisterol, a novel polyoxygenated sterol with an aromatic A ring from the tropical marine sponge Geodia sp. , 1996 .

[30]  J. Gallard,et al.  Sulfated steroids: ptilosteroids A-C and ptilosaponosides A and B from the Solomon Islands marine sponge Ptilocaulis spiculifer. , 2009, Journal of natural products.

[31]  G. Chang,et al.  Macromodel—an integrated software system for modeling organic and bioorganic molecules using molecular mechanics , 1990 .

[32]  D. Faulkner,et al.  Eurysterols A and B, cytotoxic and antifungal steroidal sulfates from a marine sponge of the genus Euryspongia. , 2007, Journal of natural products.

[33]  S. Pomponi,et al.  A new sterol sulfate, Sch 572423, from a marine sponge, Topsentia sp. , 2003, Bioorganic & medicinal chemistry letters.

[34]  F. Baldelli,et al.  Bile acid-activated receptors in the treatment of dyslipidemia and related disorders. , 2010, Progress in lipid research.

[35]  R. V. van Soest,et al.  New Antiinflammatory Sterols from the Red Sea Sponges Scalarispongia aqabaensis and Callyspongia siphonella , 2010, Natural product communications.

[36]  J. Darias,et al.  Muriceanol, A 24(28)-Epoxide Sterol Link in the Carbon Flux Toward Side-Chain Dealkylation of Sterols , 2006 .

[37]  E. Manzo,et al.  New C21 Δ20 pregnanes, inhibitors of mitochondrial respiratory chain, from Indopacific octocoral Carijoa sp. , 2004 .

[38]  G. Guella,et al.  Agnatasterone A and B, Unusual Pregnane Steroids Isolated from the North-East Atlantic Sponge Axinella agnata , 1988 .

[39]  J. Clardy,et al.  Three Pregnane-10,2-carbolactones from a Sponge, Strongylophora sp. , 1993 .

[40]  E. Fattorusso,et al.  Steroids from sponges: Recent reports , 1999, Steroids.

[41]  Arthur J. Olson,et al.  AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading , 2009, J. Comput. Chem..

[42]  K. Williams,et al.  Marine sterols IV. C21 sterols from marine sources. Identification of pregnane derivatives in extracts of the sponge . , 1977 .

[43]  S. Pomponi,et al.  Structure elucidation of a new antifungal sterol sulfate, Sch 575867, from a deep-water marine sponge (Family: Astroscleridae). , 2003, The Journal of antibiotics.

[44]  Yue‐Wei Guo,et al.  Ximaosteroids A–D, new steroids from the Hainan soft coral Scleronephthya sp. , 2009, Steroids.