Towards new ligands of nuclear receptors. Discovery of malaitasterol A, an unique bis-secosterol from marine sponge Theonella swinhoei.

@article{DeMarino2011TowardsNL,
  title={Towards new ligands of nuclear receptors. Discovery of malaitasterol A, an unique bis-secosterol from marine sponge Theonella swinhoei.},
  author={Simona De Marino and Valentina Sepe and Maria Valeria D’Auria and Giuseppe Bifulco and Barbara Renga and Sylvain Petek and Stefano Fiorucci and Angela Zampella},
  journal={Organic \& biomolecular chemistry},
  year={2011},
  volume={9 13},
  pages={
          4856-62
        }
}
Malaitasterol A, an unprecedented bis-secosterol, was isolated from a Solomon collection of Theonella swinhoei. The structure was elucidated on the basis of a combination of comprehensive 1D and 2D NMR analysis, high-resolution mass spectrometry and DFT (13)C chemical shift calculations. The biological characterization of malaitasterol A provided evidence that this compound is a potent agonist of pregnane-X-receptor and its putative binding mode to PXR has been obtained through docking… Expand
4-Methylenesterols from a Sponge Theonella swinhoei
TLDR
Three new 4-methylenesterols, theonellasterol K, acetyltheonellastersol and acetyldehydroconicasterol were isolated from the sponge Theonella swinhoei and the structures of these compounds were elucidated on the basis of their spectroscopic data and comparison of the NMR data with those of known analogues. Expand
Oxygenated Polyketides from Plakinastrella mamillaris as a New Chemotype of PXR Agonists
TLDR
Further purification of the apolar extracts of the sponge Plakinastrella mamillaris, afforded a new oxygenated polyketide named gracilioether K that represents a new chemotype of potential anti-inflammatory leads. Expand
Swinholide J, a Potent Cytotoxin from the Marine Sponge Theonella swinhoei
TLDR
Swinholide J is an unprecedented asymmetric 44-membered dilactone with an epoxide functionality in half of the molecule that displayed potent in vitro cytotoxicity against KB cells (human nasopharynx cancer) with an IC50 value of 6 nM. Expand
The First Total Synthesis of Solomonsterol B, a Marine Pregnane X Receptor Agonist
A concise route to the pregnane X receptor (PXR) agonist solomonsterol B, a natural product isolated from the marine sponge Theonella swinhoei, has been developed starting from commercially availableExpand
Anti-inflammatory cyclopeptides from the marine sponge Theonella swinhoei
Abstract DCCC chromatography followed by HPLC purification on the polar extract of marine sponge Theonella swinhoei resulted in the isolation of five new cyclopeptides, perthamides G–K. The newExpand
Preliminary Structure-Activity Relationship on Theonellasterol, a New Chemotype of FXR Antagonist, from the Marine Sponge Theonella swinhoei
Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity.Expand
Perthamides C-F, potent human antipsoriatic cyclopeptides
Abstract Two new cyclopeptides, perthamides E and F were isolated from the polar extracts of the sponge Theonella swinhoei . The new structures, featuring an unprecedented β-amino acid unit (AHMOA),Expand
Marine and Semi-Synthetic Hydroxysteroids as New Scaffolds for Pregnane X Receptor Modulation
TLDR
The isolation of a series of 24-alkylated-hydroxysteroids from the soft coral Sinularia kavarattiensis, acting as pregnane X receptor (PXR) modulators, reveals that ergost-5-en-3β-ol (4) induces PXR transactivation in HepG2 cells and stimulates the expression of the P XR target gene CYP3A4. Expand
Structural insights into Estrogen Related Receptor-β modulation: 4-Methylenesterols from Theonella swinhoei sponge as the first example of marine natural antagonists
TLDR
The first homology model of active and inactive conformations of the Estrogen Related Receptor β (ERRβ) is reported, benchmarked with the well known agonists gsk4716 and genistein, and the antagonists 4-hydroxytamoxifen and diethylstilbestrol. Expand
Insights on pregnane-X-receptor modulation. Natural and semisynthetic steroids from Theonella marine sponges.
TLDR
This study provides the molecular bases of ligand/PXR interaction useful for designing novel PXR modulators as well as investigating the effects of different modifications on ring A and on the side chain of 4-methylenesteroid derivatives toward P XR modulation. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 30 REFERENCES
Solomonamides A and B, new anti-inflammatory peptides from Theonella swinhoei.
TLDR
Two unprecedented cyclic peptides, solomonamides A and B, were isolated from the marine sponge Theonella swinhoei and showed in vivo anti-inflammatory activity and elucidated on the basis of comprehensive NMR analysis and high-resolution mass spectrometry. Expand
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.
TLDR
The identification of the first example of natural marine PXR agonists, solomonsterols A and B, from a Theonella swinhoei sponge is reported, determined by interpretation of NMR and ESIMS data. Expand
Perthamides C and D, two new potent anti-inflammatory cyclopeptides from a Solomon Lithistid sponge Theonella swinhoei
Two new metabolites, perthamides C and D, have been isolated from the marine sponge Theonella swinhoei. Their structures were determined by interpretation of NMR and ESIMS data. All compoundsExpand
7alpha-hydroxytheonellasterol, a cytotoxic 4-methylene sterol from the Philippines sponge Theonella swinhoei.
TLDR
A new 4-methylene sterol was isolated from the Philippines sponge Theonella swinhoei, along with the known compounds theonellasterol and bistheonellide A, and the structure was elucidated by interpretation of its spectroscopic data. Expand
Discovery of sulfated sterols from marine invertebrates as a new class of marine natural antagonists of farnesoid-X-receptor.
We report the biochemical characterization of sulfated polyhydroxysterols isolated from marine invertebrates as potent antagonists of farnesoid-X-receptor (FXR), a ligand-regulated transcriptionExpand
Secosteroids of marine origin
TLDR
This review describes the isolation from marine organisms of all secosteroids reported in the literature from 1972 to 2004 and gives details on the biological activities of the isolated secosteroid (e.g. antiproliferative, antifouling, antiinflammatory, antimicrobial, ichthyotoxic and antiviral). Expand
Structures of nine oxygenated 4-methylene sterols from Hachijo marine sponge Theonella swinhoei
TLDR
Nine new sterols have been isolated from a marine sponge, Theonella swinhoei, and seven sterols were found to be conicasterol derivatives oxygenated at carbon-7 and/or carbon-15. Expand
Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition.
TLDR
PXR's placement of the steroid is remarkably distinct relative to other members of the nuclear receptor superfamily, and the results provide detailed insights into the manner in which human PXR responds to a wide range of endobiotic compounds. Expand
Oxygenated 4‐Methylidene Sterols from the South China Sea Sponge Theonella swinhoei
Two new O-bearing 4-methylidene sterols, 9α-hydroxy-15-oxoconicasterol (1) and 8β-hydroxy-B-norconicasta-6α-aldehyde (2), were isolated from the EtOH extract of the marine sponge Theonella swinhoeiExpand
Dehydroconicasterol and aurantoic acid, a chlorinated polyene derivative, from the Indonesian sponge Theonella swinhoei.
The chlorinated polyene aurantoic acid (1) and the 4-methylene sterol dehydroconicasterol (2) were isolated from the Indonesian sponge Theonella swinhoei, and their structures were elucidated byExpand
...
1
2
3
...