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.
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.
Lynch
M A
MA
Laboratoire SONAS, UFR de Pharmacie, 16 boulevard Daviers, F-49100 Angers, France.
Duval
O
O
Sukhanova
A
A
Devy
J
J
MacKay
S P
SP
Waigh
R D
RD
Nabiev
I
I
D000470:Alkaloids / Q000494:pharmacology; D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053119:Benzophenanthridines; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010617:Phenanthridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000473:Alkanes; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D010617:Phenanthridines; D059004:Topoisomerase I Inhibitors; C404513:ethoxidine; C002066:fagaronine; D004247:DNA; D004264:DNA Topoisomerases, Type I