Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from Astilbe koreana

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3273-6. doi: 10.1016/j.bmcl.2006.03.036. Epub 2006 Mar 31.

Abstract

Bioassay-guided fractionation of a MeOH extract of the rhizomes of Astilbe koreana (Saxifragaceae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory assay, resulted in the isolation of a new triterpene, 3alpha,24-dihydroxyolean-12-en-27-oic acid (4), along with four triterpenes, 3-oxoolean-12-en-27-oic acid (1), 3beta-hydroxyolean-12-en-27-oic acid (beta-peltoboykinolic acid; 2), 3beta-hydroxyurs-12-en-27-oic acid (3), and 3beta,6beta-dihydroxyolean-12-en-27-oic acid (astilbic acid; 5). Compounds 1-5 inhibited PTP1B with IC50 values of 6.8+/-0.5, 5.2+/-0.5, 4.9+/-0.4, 11.7+/-0.9, and 12.8+/-1.1 microM, respectively. Our results indicate that 3-hydroxyl group and a carboxyl group in this type of triterpenes may be required for the activity, while addition of one more hydroxyl group at C-6 or C-24 may be responsible for a loss of activity. Thus, compounds 2 and 3 which possess only one hydroxyl group at C-3 and a carboxyl group at C-27 could be potential PTP1B inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Protein Tyrosine Phosphatases / metabolism
  • Saxifragaceae / chemistry*
  • Triterpenes / chemistry*
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*

Substances

  • Enzyme Inhibitors
  • Triterpenes
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases