Design and synthesis of N-methylmaleimide indolocarbazole bearing modified 2-acetamino acid moieties as Topoisomerase I inhibitors

Bioorg Med Chem Lett. 2009 Jan 15;19(2):406-9. doi: 10.1016/j.bmcl.2008.11.061. Epub 2008 Nov 21.

Abstract

A novel series of N-methylmaleimide indolocarbazole derivatives bearing modified 2-acetamino acid moieties are first reported. The cytotoxic effects of these compounds were tested in five human tumor cell lines. The potent compounds 9a, 9b, 9d, and 9e have been further evaluated for their effect on Topoisomerase I (TOPO I) and cancer cell cycle. It is concluded that the indolocarbazoles with alkyl piperazine or morpholine substituent groups instead of esters or glycosyl residues would have better activities against tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Carbazoles / chemical synthesis*
  • Carbazoles / chemistry
  • Carbazoles / pharmacology*
  • Cell Line, Tumor
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Topoisomerase I Inhibitors*

Substances

  • Amino Acids
  • Carbazoles
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors