Synthesis of novel DNA binding agents: indole-containing analogs of bis-netropsin

Mol. modeling studies showed that indole dicarboxylic acids are potential linkers for the synthesis of bisnetropsin analogs with a good fit to the minor groove of DNA. To test this hypothesis, 2-carboxyindole-6-acetic acid, indole-2,6-dicarboxylic acid, 6-(2-carboxyethyl)indole-2-carboxylic acid, and 6-(2-carboxy-1-ethenyl)indole-2-carboxylic acid were prepd. and coupled to 3-[1-methyl-4-(1-methyl-4-aminopyrrole-2-carboxamido)pyrrole-2-carboxamido]dimethylaminopropane. Similarly, indole-2,5-dicarboxylic acid was prepd. and coupled to 3-[1-methyl-4-(1-methyl-4-aminopyrrole-2-carboxamido)pyrrole-2-carboxamido]propionamidine hydrochloride. Some derivs. showed esp. strong binding at AT rich regions as shown by footprinting studies.