DNA Binding To Guide the Development of Tetrahydroindeno[1,2-b]pyrido[4,3,2-de]quinoline Derivatives as Cytotoxic Agents
| Autor: | Raymond Houssin, Michael Facompré, Nicole Pommery, Christian Bailly, Sarah Catoen-Chackal, Pierre Colson, Jean-Pierre Hénichart, Jean-François Goossens |
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| Rok vydání: | 2004 |
| Předmět: |
Stereochemistry
DNA Footprinting Antineoplastic Agents Chemical synthesis Piperazines Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery Humans Transition Temperature Molecule Fluorometry A-DNA Structural motif Circular Dichroism Quinoline DNA Chromophore Small molecule Intercalating Agents chemistry Quinolines Molecular Medicine Drug Screening Assays Antitumor Cell Division |
| Zdroj: | Journal of Medicinal Chemistry. 47:3665-3673 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm0400193 |
| Popis: | The tetrahydroindeno[1,2-b]pyrido[4,3,2-de]quinoline 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. |
| Databáze: | OpenAIRE |
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