Perthamides C-F, potent human antipsoriatic cyclopeptides

  title={Perthamides C-F, potent human antipsoriatic cyclopeptides},
  author={Carmen Festa and S. Marino and V. Sepe and M. V. D'Auria and G. Bifulco and R. M. Andr{\'e}s and M. Terencio and M. Payá and C. Debitus and A. Zampella},
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), were determined by interpretation of NMR and MS data. The absolute configuration of the AHMOA residue was proposed on the basis of quantum chemical calculation of NMR chemical shifts. Perthamides were proved to inhibit TNF-α and IL-8 release in primary human keratinocytes cells and therefore could… Expand
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
New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei
Summary Chemical analysis of the organic extract of Theonella swinhoei yielded two new tridecadepsipeptides of the theonellapeptolide family, namely sulfinyltheonellapeptolide, characterized by aExpand
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
Heat shock proteins as key biological targets of the marine natural cyclopeptide perthamide C.
The ability of perthamide C to influence heat shock protein-mediated cell apoptosis revealed that this marine metabolite could be a good candidate for the development of a lead compound with therapeutic applications based on apoptosis modulation. Expand
Natural Products from the Lithistida: A Review of the Literature since 2000
This review provides an update on the current taxonomic classification of the Lithistida, describes structures and biological activities of 131 new natural products, and discusses highlights from the total syntheses of 16 compounds from marine sponges of the Order lithiumistida providing a compilation of the literature since the last review published in 2002. Expand
4-Methylenesterols from Theonella swinhoei sponge are natural pregnane-X-receptor agonists and farnesoid-X-receptor antagonists that modulate innate immunity
It is demonstrated that swinhosterol B counter-regulates induction of pro-inflammatory cytokines in a PXR-dependent manner and pave the way to development of a dual PX R 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. Expand
Antipsoriatic natural products
Abstract Psoriasis, a chronic inflammatory skin disease, is characterized by abnormal differentiation and hyperproliferation of epidermal keratinocytes, inflammatory infiltration and increased skinExpand
Marine Natural Peptides: Determination of Absolute Configuration Using Liquid Chromatography Methods and Evaluation of Bioactivities
A literature survey covering the report on the determination of absolute configuration of the amino acid residues of diverse marine peptides by chromatographic methodologies is presented and a brief summary of their biological activities was also included emphasizing to the most promising marine peptide. Expand
Perthamide C Inhibits eNOS and iNOS Expression and Has Immunomodulating Activity In Vivo
Perthamide C selectively interferes with NO generation triggered by either eNOS or iNOS without affecting either COX-1 orCOX-2, which leads to modulation of the inflammatory response through a reduction of vascular permeability, neutrophil infiltration as well as lymphocyte proliferation. Expand
Interaction between the marine sponge cyclic peptide theonellamide A and sterols in lipid bilayers as viewed by surface plasmon resonance and solid-state (2)H nuclear magnetic resonance.
This study demonstrates that TNM-A directly recognizes the 3β-OH moiety of sterols, which greatly facilitates its binding to bilayer membranes. Expand


Solomonamides A and B, new anti-inflammatory peptides from Theonella swinhoei.
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
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
Towards new ligands of nuclear receptors. Discovery of malaitasterol A, an unique bis-secosterol from marine sponge Theonella swinhoei.
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 calculations. Expand
Concise synthesis of AHMHA unit in perthamide C. Structural and stereochemical revision of perthamide C
Abstract Diastereomers of 3-amino-2-hydroxy-6-methylheptanoic acid (AHMHA), a new amino acid unit in perthamides C and D, have been synthesized from commercially available 4-methylpentanol in aExpand
A serendipitous discovery of isomotuporin-containing sponge populations of Theonella swinhoei.
An in-depth LCMS examination of 14 different collections of Indo-Pacific Theonella swinhoei sponges resulted in the discovery of four diastereomeric analogues of the cyclic pentapeptide motuporin, all of which contain a novel 2R configuration for the Adda amino acid. Expand
Determination ofD-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene
Abstract1-fluoro-2,4-dinitrophenyl-5-l-alanine amide has been synthesized in high yield (76%) from 1,5-difluoro-2,4-dinitrobenzene andl-Ala-NH2. This compound contains a reactive fluorine atom whichExpand
Quantum Mechanical Calculation of NMR Parameters in the Stereostructural Determination of Natural Products
The present microreview highlights the recent goals reached by the application of a combined approach of NMR spectroscopy and quantum chemical methods in the structural studies of natural products.Expand
Novel immunotherapies for psoriasis.
If psoriasis is considered as a visible model disease for T-cell-mediated disorders characterized by a type-1 cytokine pattern these recent findings might have a more general impact on the treatment of autoimmune disorders. Expand
Comparisons of two in vitro cytotoxicity assays-The neutral red (NR) and tetrazolium MTT tests.
The neutral red (NR) and tetrazolium MTT in vitro cytotoxicity assays were compared for 28 test agents of widely varying potency using the BALB/c mouse 3T3 fibroblast cell line as the bioindicator and were capable of demonstrating a reduction of methotrexate by leucovorin. Expand
Biology of tumor necrosis factor‐α– implications for psoriasis
The current knowledge of TNF biology, the approaches to inhibit TNF activity, and their clinical and immunological effects in psoriasis are reviewed. Expand