DNA Binding To Guide the Development of Tetrahydroindeno1,2-bpyrido4,3,2-dequinoline Derivatives as Cytotoxic Agents

摘要

The tetrahydroindeno1,2-bpyrido4,3,2-dequinoline chromophore was initially designed as a DNA intercalating unit because of its planar structure. Unexpectedly, one molecule (15d) bearing two N-methylpiperazine chains on both sides of this condensed pentacyclic skeleton fits into the minor groove of DNA and preferentially recognizes AT-rich sequences. The monosubstituted compound 16d was identified as a potent cytotoxic DNA intercalator, whereas the disubstituted analogue 15d represents a new structural motif for the development of DNA sequence-reading small molecules.