Isolation and structure determination of novel phosphatidylinositol kinase inhibitors, echiguanines A and B, from Streptomyces sp

J Nat Prod. 1991 Sep-Oct;54(5):1321-5. doi: 10.1021/np50077a014.

Abstract

In the course of a screening program for phosphatidylinositol kinase inhibitors, we discovered novel inhibitors, echiguanines A and B, from the culture broth of a Streptomyces strain MI698-50F1 (FERMP-11563). The structures of echiguanines A and B were revealed to be N-(2-amidinoethyl)-2-amino-4-hydroxy-7H-pyrrolo[2,3- d]pyrimidine-5-carboxamide and N-(3-aminopropyl)-2-amino-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidine- 5-carboxamide, respectively, by nmr spectroscopy and X-ray crystallography. Echiguanines A and B inhibited phosphatidylinositol kinase of the A431 cell membrane with IC50's of 0.04 microgram/ml and 0.11 micrograms/ml, respectively. Echiguanine A is the most potent inhibitor of phosphatidylinositol kinase so far discovered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase
  • Cell Membrane / drug effects
  • Cell Membrane / enzymology
  • Humans
  • Molecular Structure
  • Phosphotransferases / antagonists & inhibitors*
  • Pyrimidines / chemistry
  • Pyrimidines / isolation & purification*
  • Pyrimidines / pharmacology
  • Pyrroles / chemistry
  • Pyrroles / isolation & purification*
  • Pyrroles / pharmacology
  • Streptomyces / chemistry*
  • Tumor Cells, Cultured
  • X-Ray Diffraction

Substances

  • Pyrimidines
  • Pyrroles
  • echiguanine A
  • echiguanine B
  • Phosphotransferases
  • 1-Phosphatidylinositol 4-Kinase