Synthesis, DNA-cleaving activities and cytotoxicities of C2-symmetrical dipyrrole-polyamide dimer-based Cu(II) complexes: A comparative study

•Two polyamine-tethered C2-symmetrical dipyrrole-polyamide dimers were synthesized.•They formed 1:1 complexes with Cu(II) ion.•Both complexes showed potent DNA-cleaving activities, via an oxidative mechanism.•Strong metal complexation does not necessarily enhance the catalytic efficiency.•The Cu(II) complexes displayed moderate inhibitory activities toward three tumor cell lines.

Two C2-symmetrical dipyrrole-polyamide dimers 2 and 3 that were tethered with triethylenetetramine and spermine, respectively, and their corresponding Cu(II) complexes 2@Cu2+ and 3@Cu2+, were synthesized and fully characterized. Agarose gel electrophoresis studies on pBR322 DNA cleavage indicated that both Cu(II) complexes exhibited potent DNA-cleaving activities under physiological conditions, most probably via an oxidative mechanism. Kinetic assay indicate that 2@Cu2+ and 3@Cu2+ exhibited comparable catalytic efficiency with the Cu(II) complex of their 2,2′-(ethane-1,2-diylbis(oxy))diethanamine-tethered analog 1. The finding that compounds 2 and 3 showed higher Cu(II) ion-complexing abilities than compound 1, suggests that strong metal complexation does not necessarily lead to an enhancement in the catalytic efficiency of a DNA-cleaving agent. In addition, three Cu(II) complexes displayed moderate inhibitory activities toward three tumor cell lines.

Graphical abstractThe Cu(II) complexes of polyamine-tethered C2-symmetrical dipyrrole-polyamide dimers were synthesized and found to exhibit potent DNA-cleaving activities and moderate inhibitory activities toward three tumor cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slide