Synthesis and Antitumor Activity of Staurosporine Derivatives.

Twenty-four derivatives of staurosporine were synthesized by modification at the 3′- N, 3- and 7-positions. Of these compounds, 16 were synthesized for the first time and their structures were determined by NMR spectroscopy, ECD, and HRESIMS. Their inhibitory activities against seven tumor cell lines, MV4-11 (leukemia), MCF-7 (breast carcinoma), HCT-116 (colon cancer), TE-1 (esophageal carcinoma), PATU8988 T (pancreatic cancer), HOS (osteosarcoma) and GBC-SD (gallbladder cancer), and human normal liver cell L-02 were evaluated using a Cell Counting Kit-8. The IC₅₀ values for 7-oxo-3′- N -benzoylstaurosporin (4) on MV4-11 and PATU8988 T cells were 0.078 and 0.666 μmol/L, and the selection indexes were 1254 and 147, respectively. The IC₅₀ values of 7-oxo-3-chloro-3′- N -benzoylstaurosporine (5) and (7 R)-7-hydroxy-3-bromo-3′- N -acetylstaurosporine (24) on MCF-7 cells were 0.029 and 0.021 μmol/L, and the selection indexes were 102 and 221, respectively. The above compounds have the potential to be developed further into antitumor drugs due to the advantages of high efficiency and low toxicity. [ABSTRACT FROM AUTHOR]