UCN-01 and UCN-02, new selective inhibitors of protein kinase C. II. Purification, physico-chemical properties, structural determination and biological activities.
A new inhibitor of protein kinase C (PKC), UCN-01, was isolated from the culture broth of Streptomyces sp. N-126. We have found that this strain also produces UCN-02 which is a stereoisomer of UCN-01. The inhibitors have the molecular formula C28H26N4O4 and have an indolo[2,3-alpha]carbazole chromophore. Their structures have been elucidated by mass and NMR spectra. UCN-01 has been shown to inhibit PKC and protein kinase A (PKA) with IC50 values of 0.0041 and 0.042 microM, respectively, and UCN-02 has been shown to inhibit PKC and PKA with IC50 values of 0.062 and 0.25 microM, respectively. UCN-01 and UCN-02 also showed the cytotoxic effect on the growth of HeLa S3 cells.
Takahashi
I
I
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan.
Saitoh
Y
Y
Yoshida
M
M
Sano
H
H
Nakano
H
H
Morimoto
M
M
Tamaoki
T
T
D000470:Alkaloids / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006367:HeLa Cells; D006801:Humans; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000031:analogs & derivatives
D000470:Alkaloids; C054852:7-hydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine