Semi-synthesis, topoisomerase I and kinases inhibitory properties, and antiproliferative activities of new rebeccamycin derivatives

Bioorg Med Chem. 2003 Nov 17;11(23):4871-9. doi: 10.1016/j.bmc.2003.09.014.


In the course of structure-activity relationship studies, new rebeccamycin derivatives substituted in 3,9-positions on the indolocarbazole framework, and a 2',3'-anhydro derivative were prepared by semi-synthesis from rebeccamycin. The antiproliferative activities against nine tumor cell lines were determined and the effect on the cell cycle of murine leukemia L1210 cells was examined. Their DNA binding properties and inhibitory properties toward topoisomerase I and three kinases PKCzeta, CDK1/cyclin B, CDK5/p25 and a phosphatase cdc25A were evaluated. The 3,9-dihydroxy derivative is the most efficient compound of this series toward CDK1/cyclin B and CDK5/p25. It is also characterized as a DNA binding topoisomerase I poison. Its broad spectrum of molecular activities likely accounts for its cytotoxic potential. This compound which displays a tumor cell line-selectivity may represent a new lead for subsequent drug design in this series of glycosylated indolocarbazoles.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / chemical synthesis*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Phosphotransferases / antagonists & inhibitors*
  • Spectrum Analysis
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors*


  • Antineoplastic Agents
  • Carbazoles
  • Enzyme Inhibitors
  • Indoles
  • Topoisomerase I Inhibitors
  • rebeccamycin
  • Phosphotransferases