Synthesis, biological activity and comparative analysis of DNA binding affinities and human DNA topoisomerase I inhibitory activities of novel 12-alkoxy-benzo[c]phenanthridinium salts

Bioorg Med Chem Lett. 2001 Oct 8;11(19):2643-6. doi: 10.1016/s0960-894x(01)00520-0.

Abstract

New antitumor 12-alkoxy-benzo[c]phenanthridinium derivatives were obtained in high yields through multistep syntheses. Analysis of DNA binding and human DNA topoisomerase I inhibitory activities demonstrates that new compounds, combining 2, 6, and 12 substitutions, interact strongly with DNA and exhibit important topoisomerase I inhibition. The cytotoxicities against solid tumor cell lines are also determined and compared with those for fagaronine and ethoxidine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Alkanes / chemical synthesis
  • Alkanes / chemistry
  • Alkanes / pharmacology*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Benzophenanthridines
  • DNA / drug effects*
  • DNA / metabolism
  • DNA Topoisomerases, Type I / metabolism
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Phenanthridines / chemical synthesis
  • Phenanthridines / chemistry
  • Phenanthridines / pharmacology*
  • Topoisomerase I Inhibitors*
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • Alkanes
  • Antineoplastic Agents
  • Benzophenanthridines
  • Enzyme Inhibitors
  • Phenanthridines
  • Topoisomerase I Inhibitors
  • ethoxidine
  • fagaronine
  • DNA
  • DNA Topoisomerases, Type I