Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors

In the context of the design and synthesis of minor groove binding and intercalating DNA ligands some new oligopyrrole carboxamides were synthesized. These hybrid molecules (combilexins) possess a variable and conformatively flexible spacer at the N-terminal end. As intercalating tricyclic systems acridone, acridine, anthraquinones and in a special case iminostilbene terminate the N-terminal end of the pyrrole chain. The cytotoxicity was examined by the NCI antitumor screening, furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA binding properties and topoisomerase inhibition effect of this new series of molecules.

Design, synthesis and biological evaluation of a new class of very interesting hybrid molecules closely related to the natural antibiotic netropsin as potential DNA ligands were described. These hybrid compounds consist of a propylamin-pyrrole-carboxamide core as a minor groove binding element linked by a conformatively flexible aliphatic spacer with a tricyclic intercalator at the N-terminal end.Figure optionsDownload as PowerPoint slide