Protein Tyrosine Phosphatase 1B Inhibitory Iridoids from Psydrax subcordata

J Nat Prod. 2019 Oct 25;82(10):2916-2924. doi: 10.1021/acs.jnatprod.9b00770. Epub 2019 Oct 16.

Abstract

Phytochemical investigation of the leaves and bark of Psydrax subcordata has led to the isolation of six new iridoids, subcordatanols I-V (1-4 and 6) and 1-O-methylcrescentin I (5), along with two known analogues (7 and 8). Among them, subcordatanol I (1) is the first example of a 3,8-monoepoxy-iridoid featuring a caged 2-oxa-bicyclo[3.2.1]octane core. The absolute stereochemistry at C-4 of 3, 4, and 6 was established through their acid-catalyzed reaction products subcordatalactones A (3a), B (4a), and C (6a), respectively. Subcordatanols I (1) and II (2), as well as subcordatalactones A (3a) and B (4a), displayed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Enzyme kinetic studies indicated that 3a and 4a are competitive inhibitors. A molecular docking study is also reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Iridoids / chemistry
  • Iridoids / isolation & purification*
  • Iridoids / pharmacology
  • Magnetic Resonance Spectroscopy
  • Molecular Docking Simulation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Rubiaceae / chemistry*

Substances

  • Iridoids
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1