Trichoketides A and B, two new protein tyrosine phosphatase 1B inhibitors from the marine-derived fungus Trichoderma sp

J Antibiot (Tokyo). 2015 Oct;68(10):628-32. doi: 10.1038/ja.2015.44. Epub 2015 Apr 22.

Abstract

Two new octaketides, trichoketides A (1) and B (2), were isolated from a culture broth of the seawater-derived fungus Trichoderma sp. TPU1237 together with two known analogs, trichodermaketones C (3) and D (4), by ODS column chromatography followed by preparative ODS and chiral HPLC. The structures of 1 and 2 were elucidated on the basis of their spectroscopic data, and absolute configurations were assigned by comparing their experimental electronic circular dichroism (ECD) spectra with the calculated ECD spectra. Compounds 1 and 2 were epimers at the C-8 position (α-position of dihydrofuran ring). The IC50 values of compounds 1-4 against protein tyrosine phosphatase 1B were 53.1, 65.1, 68.0 and 55.9 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Fermentation
  • Molecular Conformation
  • Polyketides / chemistry
  • Polyketides / isolation & purification*
  • Polyketides / pharmacology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Seawater / microbiology
  • Trichoderma / chemistry*

Substances

  • Enzyme Inhibitors
  • Polyketides
  • trichoketide A
  • trichoketide B
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1