Protein tyrosine phosphatase 1B inhibitory effects of depsidone and pseudodepsidone metabolites from the Antarctic lichen Stereocaulon alpinum

Bioorg Med Chem Lett. 2009 May 15;19(10):2801-3. doi: 10.1016/j.bmcl.2009.03.108. Epub 2009 Mar 26.

Abstract

Seven phenolic lichen metabolites (1-7) have been isolated from a methanol extract of the Antarctic lichen Stereocaulon alpinum by various chromatographic methods. The structures of these compounds were determined mainly by analysis of NMR spectroscopic data. A depsidone-type compound, lobaric acid (1) and two pseudodepsidone-type compounds, 2 and 3, exhibited potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC(50) values of 0.87microM, 6.86microM, and 2.48microM, respectively. Kinetic analyses of PTP1B inhibition by compounds 1 and 2 suggested that these compounds inhibited PTP1B activity in a non-competitive manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Depsides / chemistry
  • Depsides / isolation & purification
  • Depsides / metabolism*
  • Depsides / pharmacology
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Kinetics
  • Lactones / chemistry*
  • Lactones / isolation & purification
  • Lactones / metabolism*
  • Lactones / pharmacology
  • Lichens / chemistry*
  • Lichens / metabolism
  • Plant Extracts / chemistry
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Salicylates / chemistry*
  • Salicylates / isolation & purification
  • Salicylates / pharmacology

Substances

  • Depsides
  • Enzyme Inhibitors
  • Lactones
  • Plant Extracts
  • Salicylates
  • depsidone
  • lobaric acid
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1