Carteriosulfonic acids A-C, GSK-3beta inhibitors from a Carteriospongia sp

J Nat Prod. 2009 Sep;72(9):1651-6. doi: 10.1021/np900336f.

Abstract

Modulators of Wnt signaling have therapeutic potential in a number of human diseases. A fractionated library from marine invertebrates was screened in a luciferase assay designed to identify modulators of Wnt signaling. A fraction from a Carteriospongia sp. sponge activated Wnt signaling and was subsequently shown to inhibit GSK-3beta, which inhibits Wnt signaling through phosphorylation of beta-catenin. Three novel natural products, carteriosulfonic acids A (1), B (2), and C (3), were identified as active constituents. The carteriosulfonic acids contain unprecedented 4,6,7,9-tetrahydroxylated decanoic acid subunits. Their structures were elucidated through analysis of NMR data and a detailed analysis of pseudo MS(3) spectra.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Marine Biology
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Oceans and Seas
  • Porifera / chemistry*
  • Sulfonic Acids / chemistry
  • Sulfonic Acids / isolation & purification*
  • Sulfonic Acids / pharmacology*
  • Wnt Proteins / drug effects
  • Wnt Proteins / metabolism*

Substances

  • Sulfonic Acids
  • Wnt Proteins
  • carteriosulfonic acid A
  • carteriosulfonic acid B
  • carteriosulfonic acid C
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3