Protein tyrosine phosphatase 1B inhibitory activities of ursane- and lupane-type triterpenes from Sorbus pohuashanensis

J Nat Med. 2014 Apr;68(2):427-31. doi: 10.1007/s11418-013-0804-x. Epub 2013 Oct 6.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase, and has received much attention as a molecular target for the treatment of insulin resistance diseases because of its critical roles in negatively regulating insulin- and leptin-signaling cascades. Six ursane-type triterpenes, 3β-acetoxy-urs-12-ene-28-oic acid (1), pomolic acid-3β-acetate (2), pomolic acid (3), ursolaldehyde (4), euscaphic acid (5) and 3β-acetoxy-urs-11-en-28,13-olide (6), and a lupane-type triterpene, betulinic acid (7), from the fruits of Sorbus pohuashanensis, exhibited significant PTP1B inhibitory activity, with IC50 values ranging from 3.5 to 54.8 μM. Kinetics analyses revealed that compounds 2, 3, and 7 are non-competitive PTP1B inhibitors, and compounds 1 and 6 are mixed-type PTP1B inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Sorbus / chemistry*
  • Triterpenes / chemistry*
  • Triterpenes / pharmacology*

Substances

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