Synthesis of novel DNA binding agents: Indole-containing analogues of bis-netropsin

Molecular modelling studies showed that indole dicarboxylic acids are potential linkers for the synthesis of bisnetropsin analogues 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, 6-(2-carboxy-1-ethenyl)indole-2-carboxylic acid were prepared and coupled to 3-[1-methyl-4-(1-methyl-4-aminopyrrole-2-carboxamido)pyrrole-2- carboxamido]dimethylaminopropane. Similarly indole-2,5-dicarboxylic acid was prepared and coupled to 3-[1-methyl-4-(1-methy-4-aminopyrrple-2- carboxamido)pyrrole-2-carboxamido]propionamidine hydrochloride. The derivatives of 26-28 showed especially strong binding to AT rich regions as shown by footprinting studies.