Isolation and Structure Determination of Novel Phosphatidylinositol Kinase Inhibitors, Echiguanines A and B, from Streptomyces sp.

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.