Oligopyrrole carboxamides linked with a nucleobase as potential DNA minor groove binding ligands: synthesis, DNA binding and biological evaluation.

The synthesis of a series of new oligopyrrole carboxamides closely related to netropsin and distamycin A, linked with a nucleobase is reported. The new compounds possess similar structure elements as the known peptide nucleic acids which are interesting sequence reading DNA ligands. Cytotoxicity in vitro, the DNA binding characteristics and the inhibition of topoisomerase I were studied. Four of the compounds, 27, 31, 33 and 37 bind to DNA probably at AT sequences like netropsin or distamycin A in the minor groove. Surprisingly, no cytotoxicity and no inhibition of topoisomerase I was found.