| Abstract
| - New azaquinolizinium-type cations have been obtained from isochromane. The synthesis wascompleted over seven steps and included as the key feature an intramolecular Westphalcondensation. This first example of the intramolecular process allowed the preparation of benzo[f]pyrido[2,1-a]phthalazinium and benzo[f]quino[2,1-a]phthalazinium salts, which were evaluated as DNA intercalators, DNA topoisomerase I inhibitors, and antiproliferative compounds.Both cationic systems behave as DNA intercalators and exhibit antiproliferative activity. Thepentacyclic benzo[f]quino[2,1-a]phthalazinium cations also have an inhibitory effect on thecatalytic activity of DNA topoisomerase I, without trapping of cleavage complexes. Structuralcharacterization using density functional theory indicates that the fused ring systems areslightly nonplanar, and additional molecular modeling studies suggest a preferred orientationfor the intercalating chromophores within a typical CpG or TpG intercalation site.
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