Isolation of a novel protein tyrosine phosphatase inhibitor, 2-methyl-fervenulone, and its precursors from Streptomyces

J Nat Prod. 2000 Dec;63(12):1641-6. doi: 10.1021/np000293+.

Abstract

High-throughput screening identified an extract from Streptomyces sp. IM 2096 with inhibitory activity toward several protein tyrosine phosphatases (PTPs). Four 1,2,4-triazine compounds 2096A-D (1-4) were isolated from this extract and their structures elucidated by interpretation of spectroscopic data and confirmed by degradation and synthesis. The novel glycocyamidine derivatives 1 and 2 are diastereomers and may interconvert. Both are inactive in the PTP inhibition assay. Compounds 1 and 2 are unstable and partially decompose to 3 and glycocyamidine (5) at room temperature. Compound 3, known as MSD-92 or 2-methyl-fervenulone, is a broad-specificity PTP inhibitor with comparable potency to vanadate. The imidazo[4, 5-e]-1,2,4-triazine (4), inactive in the PTP-inhibition assay, may be a degradation product of 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • Molecular Structure
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Spectrum Analysis
  • Streptomyces / enzymology*
  • Triazines / chemistry
  • Triazines / isolation & purification*
  • Triazines / pharmacology

Substances

  • 2-methyl-fervenulone
  • Enzyme Inhibitors
  • Triazines
  • Protein Tyrosine Phosphatases