Isolation and structure determination of novel phosphatidylinositol kinase inhibitors, echiguanines A and B, from Streptomyces sp.
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.
Nishioka
H
H
Institute of Microbial Chemistry, Tokyo, Japan.
Sawa
T
T
Nakamura
H
H
Iinuma
H
H
Ikeda
D
D
Sawa
R
R
Naganawa
H
H
Hayashi
C
C
Hamada
M
M
Takeuchi
T
T
D019870:1-Phosphatidylinositol 4-Kinase; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D015394:Molecular Structure; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014961:X-Ray Diffraction
D011743:Pyrimidines; D011758:Pyrroles; C073630:echiguanine A; C073632:echiguanine B; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase