Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Cell Division / drug effects
-
Cell Line, Tumor
-
Circular Dichroism
-
DNA / chemistry*
-
DNA Footprinting
-
Drug Screening Assays, Antitumor
-
Fluorometry
-
Humans
-
Intercalating Agents / chemical synthesis
-
Intercalating Agents / chemistry
-
Intercalating Agents / pharmacology
-
Piperazines / chemical synthesis*
-
Piperazines / chemistry
-
Piperazines / pharmacology
-
Quinolines / chemical synthesis*
-
Quinolines / chemistry
-
Quinolines / pharmacology
-
Structure-Activity Relationship
-
Transition Temperature
Substances
-
4,5-dimethoxy-10-(3-(4-methyl)piperazin-1-ylpropoxy)-1,2,3,12-tetrahydroindeno(1,2-b)pyrido(4,3,2-de)quinoline
-
4,5-dimethoxy-3-(2-(4-methyl)piperazin-1-ylacetyl)-10-(3-(4-methyl)piperazin-1-ylpropoxy)-1,2,3,12-tetrahydroindeno(1,2-b)pyrido(4,3,2-de)quinoline
-
Antineoplastic Agents
-
Intercalating Agents
-
Piperazines
-
Quinolines
-
DNA