title: 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.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishioka
authors.forename: T
authors.initials: T
authors.lastname: Sawa
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Iinuma
authors.forename: D
authors.initials: D
authors.lastname: Ikeda
authors.forename: R
authors.initials: R
authors.lastname: Sawa
authors.forename: H
authors.initials: H
authors.lastname: Naganawa
authors.forename: C
authors.initials: C
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Hamada
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: 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
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; C073630:echiguanine A; C073632:echiguanine B; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase