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.
Fiche publication
Date publication
octobre 2001
Journal
Bioorganic & medicinal chemistry letters
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DEVY Jérôme, Pr NABIEV Igor
Tous les auteurs :
Lynch MA, Duval O, Sukhanova A, Devy J, MacKay SP, Waigh RD, Nabiev I
Lien Pubmed
Résumé
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.
Mots clés
Alkaloids, pharmacology, Alkanes, chemical synthesis, Antineoplastic Agents, chemical synthesis, Benzophenanthridines, DNA, drug effects, DNA Topoisomerases, Type I, metabolism, Drug Screening Assays, Antitumor, Enzyme Inhibitors, pharmacology, Humans, Phenanthridines, chemical synthesis, Topoisomerase I Inhibitors, Tumor Cells, Cultured
Référence
Bioorg. Med. Chem. Lett.. 2001 Oct;11(19):2643-6