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.
M A Lynch  1 ,  O Duval ,  A Sukhanova ,  J Devy ,  S P MacKay ,  R D Waigh ,  I Nabiev
Affiliations
  • 1. Laboratoire SONAS, UFR de Pharmacie, 16 boulevard Daviers, F-49100 Angers, France.
PMID: 11551768 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.