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-a]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 μM, respectively, and UCN-02 has been shown to inhibit PKC and PKA with IC50 values of 0.062 and 0.25 μM, respectively. UCN-01 and UCN-02 also showed the cytotoxic effect on the growth of HeLa S3 cells.