Preliminary structure-activity relationship on theonellasterol, a new chemotype of FXR antagonist, from the marine sponge Theonella swinhoei

Marine Drugs

Volumn 10, Issue 11, 2012, Pages 2448-2466

  Sepe, Valentina ^a   Ummarino, Raffaella ^a   D'Auria, Maria Valeria ^a   Taglialatela Scafati, Orazio ^a   De Marino, Simona ^a   D'Amore, Claudio ^b   Renga, Barbara ^b   Chini, Maria Giovanna ^c   Bifulco, Giuseppe ^c   Nakao, Yoichi ^d   Fusetani, Nobuhiro ^d   Fiorucci, Stefano ^b   Zampella, Angela ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b UNIVERSITY OF PERUGIA   (Italy)

^c UNIVERSITY OF SALERNO   (Italy)

^d WASEDA UNIVERSITY   (Japan)

Author keywords

Chemical modification; Farnesoid X receptor; Marine sponges; Nuclear receptors; Steroids; Structure activity relationship; Theonella swinhoei; Theonellasterol

Indexed keywords

24 ETHYL 3BETA HYDROXYL 5ALPHA CHOLEST 4 ONE; 24 ETHYL 4 METHYL 5ALPHA CHOLEST 3 ENE; 24 ETHYL 4ALPHA METHYL 5ALPHA CHOLESTAN 3 ONE; 24 ETHYL 4ALPHA METHYL 5ALPHA CHOLESTAN 3ALPHA OL; 24 ETHYL 4ALPHA METHYL 5ALPHA CHOLESTAN 3BETA OL; 24 ETHYL 4BETA METHYL 5ALPHA CHOLESTAN 3 ONE; 24 ETHYL 4BETA METHYL 5ALPHA CHOLESTAN 3ALPHA OL; 24 ETHYL 4BETA METHYL 5ALPHA CHOLESTAN 3BETA OL; 24 ETHYL 5ALPHA CHOLESTAN 3BETA,4BETA DIOL; 3BETA O ACETYL THEONELLASTEROL; 3BETA O METHYL THEONELLASTEROL; CHENODEOXYCHOLIC ACID; FARNESOID X RECEPTOR ANTAGONIST; HORMONE RECEPTOR BLOCKING AGENT; HYDROXYL GROUP; THEONELLASTEROL; THEONELLASTERONE; UNCLASSIFIED DRUG;

ARTICLE; CELL STRAIN HEPG2; CHEMICAL BOND; CHEMICAL MODIFICATION; DRUG ISOLATION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MOLECULAR DOCKING; MOLECULAR INTERACTION; NONHUMAN; OXIDATION; RECEPTOR BLOCKING; RECEPTOR DOWN REGULATION; STRUCTURE ACTIVITY RELATION; THEONELLA; THEONELLA SWINHOEI; TRANSACTIVATION;

EID: 84870003556     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md10112448     Document Type: Article

References (35)

1. Kho, E.; Imagawa, D.K.; Rohmer, M.; Kashman, Y.; Djerassi, C. Sterols in marine invertebrates. 22. Isolation and structure elucidation of conicasterol and theonellasterol, two new 4-methylene sterols from the Red Sea sponges Theonella conica and Theonella swinhoei. J. Org. Chem. 1981, 46, 1836-1839.
2. Festa, C.; De Marino, S.; Sepe, V.; Monti, M.C.; Luciano, P.; D'Auria, M.V.; Debitus, C.; Bucci, M.; Vellecco, V.; Zampella, A. Perthamides C and D, two new potent anti-inflammatory cyclopeptides from a Solomon Lithistid sponge Theonella swinhoei. Tetrahedron 2009, 65, 10424-10429.
3. Margarucci, L.; Monti, M.C.; Mencarelli, A.; Fiorucci, S.; Riccio, R.; Zampella, A.; Casapullo, A. Heat shock proteins as key biological targets of the marine natural cyclopeptide perthamide C. Mol. BioSyst. 2012, 8, 1412-1417.
4. Sepe, V.; D'Auria, M.V.; Bifulco, G.; Ummarino, R.; Zampella, A. Concise synthesis of AHMHA unit in perthamide C. Structural and stereochemical revision of perthamide C. Tetrahedron 2010, 66, 7520-7526.
5. Festa, C.; De Marino, S.; Sepe, V.; D'Auria, M.V.; Bifulco, G.; Andres, R.; Terencio, M.C.; Paya, M.; Debitus, C.; Zampella, A. Perthamides C-F, potent human antipsoriatic cyclopeptides. Tetrahedron 2011, 67, 7780-7786.
6. Festa, C.; De Marino, S.; D'Auria, M.V.; Monti, M.C.; Bucci, M.; Vellecco, V.; Debitus, C.; Zampella, A. Anti-Inflammatory cyclopeptides from the marine sponge Theonella swinhoei. Tetrahedron 2012, 68, 2851-2857.
7. Festa, C.; De Marino, S.; Sepe, V.; D'Auria, M.V.; Bifulco, G.; Debitus, C.; Bucci, M.; Vellecco, V.; Zampella, A. Solomonamides A and B, new anti-inflammatory peptides from Theonella swinhoei. Org. Lett. 2011, 13, 1532-1535.
8. Festa, C.; De Marino, S.; D'Auria, M.V.; Bifulco, G.; Renga, B.; Fiorucci, S.; Petek, S.; Zampella, A. 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. J. Med. Chem. 2011, 54, 401-405.
9. Sepe, V.; Ummarino, R.; D'Auria, M.V.; Mencarelli, A.; D'Amore, C.; Renga, B.; Zampella, A.; Fiorucci, S. Total synthesis and pharmacological characterization of solomonsterol A, a potent marine pregnane-X-receptor agonist endowed with anti-inflammatory activity. J. Med. Chem. 2011, 54, 4590-4599.
10. Sepe, V.; Ummarino, R.; D'Auria, M.V.; Renga, B.; Fiorucci, S.; Zampella, A. The first total synthesis of solomonsterol B, a marine pregnane X receptor agonist. Eur. J. Org. Chem. 2012, 27, 5187-5194.
11. Sepe, V.; Ummarino, R.; D'Auria, M.V.; Lauro, G.; Bifulco, G.; D'Amore, C.; Renga, B.; Fiorucci, S.; Zampella, A. Modification in the side chain of solomonsterol A: Discovery of cholestan disulfate as a potent pregnane-X-receptor agonist. Org. Biomol. Chem. 2012, 10, 6350-6362.
12. De Marino, S.; Festa, C.; D'Auria, M.V.; Cresteil, T.; Debitus, C.; Zampella, A. Swinholide J, a potent cytotoxin from the marine sponge Theonella swinhoei. Mar. Drugs 2011, 9, 1133-1141.
13. De Marino, S.; Ummarino, R.; D'Auria, M.V.; Chini, M.G.; Bifulco, G.; Renga, B.; D'Amore, C.; Fiorucci, S.; Debitus, C.; Zampella, A. Theonellasterols and conicasterols from Theonella swinhoei. Novel marine natural ligands for human nuclear receptors. J. Med. Chem. 2011, 54, 3065-3075.
14. De Marino, S.; Sepe, V.; D'Auria, M.V.; Bifulco, G.; Renga, B.; Petek, S.; Fiorucci, S.; Zampella, A. Towards new ligands of nuclear receptors. Discovery of malaitasterol A, an unique bis-secosterol from marine sponge Theonella swinhoei. Org. Biomol. Chem. 2011, 9, 4856-4862.
15. Sepe, V.; Ummarino, R.; D'Auria, M.V.; Chini, M.G.; Bifulco, G.; Renga, B.; D'Amore, C.; Debitus, C.; Fiorucci, S.; Zampella, A. Conicasterol E, a small heterodimer partner sparing farnesoid X receptor modulator endowed with a pregnane X receptor agonistic activity, from the marine sponge Theonella swinhoei. J. Med. Chem. 2012, 55, 84-93.
16. Chini, M.G.; Jones, C.R.; Zampella, A.; D'Auria, M.V.; Renga, B.; Fiorucci, S.; Butts, C.P.; Bifulco, G. Quantitative NMR-derived interproton distances combined with quantum mechanical calculations of 13C chemical shifts in the stereochemical determination of conicasterol F, a nuclear receptor ligand from Theonella swinhoei. J. Org. Chem. 2012, 77, 1489-1496.
17. De Marino, S.; Ummarino, R.; D'Auria, M.V.; Chini, M.G.; Bifulco, G.; D'Amore, C.; Renga, B.; Mencarelli, A.; Petek, S.; Fiorucci, S.; Zampella, A. 4-Methylenesterols from Theonella swinhoei sponge are natural pregnane-X-receptor agonists and farnesoid-X-receptor antagonists that modulate innate immunity. Steroids 2012, 77, 484-495.
18. Fiorucci, S.; Distrutti, E.; Bifulco, G.; D'Auria, M.V.; Zampella, A. Marine sponge steroids as nuclear receptor ligands. Trends Pharmacol. Sci. 2012, 33, 591-601.
19. Pellicciari, R.; Costantino, G.; Fiorucci, S. Farnesoid X receptor: From structure to potential clinical applications. J. Med. Chem. 2005, 48, 5383-5403. (Pubitemid 41209235)
20. Fiorucci, S.; Rizzo, G.; Donini, A.; Distrutti, E.; Santucci, L. Targeting farnesoid X receptor for liver and metabolic disorders. Trends Mol. Med. 2007, 13, 298-309. (Pubitemid 47017005)
21. Sonoda, J.; Xie, W.; Rosenfeld, J.M.; Barwick, J.L.; Guzelian, P.S.; Evans, R.M. Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR). Proc. Natl. Acad. Sci. USA 2002, 99, 13801-13806. (Pubitemid 35215461)
22. Guo, G.L.; Lambert, G.; Negishi, M.; Ward, J.M.; Brewer, H.B.J.; Kliewer, S.A.; Gonzalez, F.J.; Sinal, C.J. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. J. Biol. Chem. 2003, 278, 45062-45071. (Pubitemid 37432638)
23. Fiorucci, S.; Cipriani, S.; Mencarelli, A.; Baldelli, F.; Bifulco, G.; Zampella, A. Farnesoid X receptor agonist for the treatment of liver and metabolic disorders: Focus on 6-ethyl-CDCA. Mini Rev. Med. Chem. 2011, 11, 753-762.
24. Kakizaki, S.; Takizawa, D.; Tojima, H.; Horiguchi, N.; Yamazaki, Y.; Mori, M. Nuclear receptors CAR and PXR; therapeutic targets for cholestatic liver disease. Front Biosci. 2011, 17, 2988-3005.
25. Fiorucci, S.; Zampella, A.; Distrutti, E. Development of FXR, PXR and CAR agonists and antagonists for treatment of liver disorders. Curr. Top. Med. Chem. 2012, 6, 605-624.
26. Poupon, R.E.; Bonnand, A.M.; Chrétien, Y.; Poupon, R. Ten-Year survival in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. Hepatology 1999, 29, 1668-1671. (Pubitemid 29247037)
27. Parés, A.; Caballería, L.; Rodés, J. Excellent long-term survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastroenterology 2006, 130, 715-720. (Pubitemid 43374522)
28. Renga, B.; Mencarelli, A.; D'Amore, C.; Cipriani, S.; D'Auria, M.V.; Sepe, V.; Chini, M.G.; Monti, M.C.; Bifulco, G.; Zampella, A.; Fiorucci, S. Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis. PLoS One 2012, 7, e30443.
29. Sepe, V.; Bifulco, G.; Renga, B.; D'Amore, C.; Fiorucci, S.; Zampella, A. Discovery of sulfated sterols from marine invertebrates as a new class of marine natural antagonists of farnesoid-X-receptor. J. Med. Chem. 2011, 54, 1314-1320.
30. D'Auria, M.V.; Sepe, V.; Zampella, A. Natural ligands for nuclear receptors: Biology and potential therapeutic applications. Curr. Top. Med. Chem. 2012, 12, 637-690.
31. Pellicciari, R.; Gioiello, A.; Costantino, G.; Sadeghpour, B.M.; Rizzo, G.; Meyer, U.; Parks, D.J.; Entrena-Guadix, A.; Fiorucci, S. Back door modulation of the farnesoid X receptor: Design, synthesis, and biological evaluation of a series of side chain modified chenodeoxycholic acid derivatives. J. Med. Chem. 2006, 49, 4208-4215. (Pubitemid 44036664)
32. Mi, L.Z.; Devarakonda, S.; Harp, J.M.; Han, Q.; Pellicciari, R.; Willson, T.M.; Khorasanizadeh, S.; Rastinejad, F. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol. Cell 2003, 11, 1093-1100. (Pubitemid 36566329)
33. Schmidt, A.W.; Doert, T.; Goutal, S.; Gruner, M.; Mende, F.; Kurzchalia, T.V.; Knölker, H.J. Regio- and stereospecific synthesis of cholesterol derivatives and their hormonal activity in Caenorhabditis elegans. Eur. J. Org. Chem. 2006, 16, 3687-3706.
34. Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009, 30, 2785-2791.
35. Sanner, M.F. A programming language for software integration and development. J. Mol. Graphics 1999, 17, 57-61. (Pubitemid 30029318)