Total synthesis and pharmacological characterization of solomonsterol A, a potent marine pregnane-X-receptor agonist endowed with anti-inflammatory activity

J Med Chem. 2011 Jul 14;54(13):4590-9. doi: 10.1021/jm200241s. Epub 2011 Jun 3.


Recently, we reported the identification of a novel class of pregnane-X-receptor (PXR) agonists, solomonsterols A and B, isolated from the marine sponge Theonella swinhoei. Preliminary pharmacological studies demonstrated that these natural compounds are potential leads for the treatment of human disorders characterized by dysregulation of innate immunity. In this article, we describe the first total synthesis of solomonsterol A and its in vivo characterization in animal models of colitis. Using transgenic mice expressing the human PXR, we found that administration of synthetic solomonsterol A effectively protects against development of clinical signs and symptoms of colitis and reduced the generation of TNFα, a signature cytokine for this disorder. In addition, we have provided the first evidence that solomonsterol A might act by triggering the expression of TGFβ and IL-10, potent counter-regulatory cytokines in inflammatory bowel diseases (IBD). Finally, we have shown that solomonsterol A inhibits NF-κB activation by a PXR dependent mechanism. In summary, solomonsterol A is a marine PXR agonist that holds promise in the treatment of inflammation-driven immune dysfunction in clinical settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Aquatic Organisms
  • Cholanes / chemical synthesis*
  • Cholanes / chemistry
  • Cholanes / pharmacology
  • Colitis / immunology
  • Colitis / pathology
  • Colitis / prevention & control
  • Colon / drug effects
  • Colon / immunology
  • Colon / pathology
  • Humans
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology
  • Interleukin-10 / biosynthesis
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Pregnane X Receptor
  • Receptors, Steroid / agonists*
  • Receptors, Steroid / genetics
  • Sulfuric Acid Esters / chemical synthesis*
  • Sulfuric Acid Esters / chemistry
  • Sulfuric Acid Esters / pharmacology
  • Theonella*
  • Transcriptional Activation
  • Transforming Growth Factor beta / biosynthesis
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Anti-Inflammatory Agents
  • Cholanes
  • Immunologic Factors
  • Lipopolysaccharides
  • NF-kappa B
  • Pregnane X Receptor
  • Receptors, Steroid
  • Sulfuric Acid Esters
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • cholan-2,3,24-tryl-2,3,24-trisulfate
  • Interleukin-10