Caged xanthones displaying protein tyrosine phosphatase 1B (PTP1B) inhibition from Cratoxylum cochinchinense

Bioorg Chem. 2018 Aug:78:39-45. doi: 10.1016/j.bioorg.2018.02.026. Epub 2018 Mar 7.

Abstract

Four new caged xanthones (1-4) and two known compounds (5, 6) were isolated from the roots of Cratoxylum cochinchinense, a polyphenol rich plant, collected in China. The structures of the isolated compounds (1-6) were characterized by obtaining their detailed spectroscopic data. In particular, compounds 1 and 6 were fully identified by X-ray crystallographic data. The isolated compounds (1-6) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer. Among these compounds, 3, 4, and 6 displayed significant inhibition with IC50 values of 76.3, 43.2, and 6.6 µM, respectively. A detailed kinetic study was conducted by determining Km, Vmax, and the ratio of Kik and Kiv, which revealed that all the compounds behaved as competitive inhibitors.

Keywords: Caged xanthones; Cratoxylum cochinchinense; Protein tyrosine phosphatase 1B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clusiaceae / chemistry*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Structure-Activity Relationship
  • Xanthones / chemical synthesis
  • Xanthones / chemistry
  • Xanthones / pharmacology*

Substances

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