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

Abstract

Two C₂-symmetrical dipyrrole-polyamide dimers 2 and 3 that were tethered with triethylenetetramine and spermine, respectively, and their corresponding Cu(II) complexes 2@Cu(2+) and 3@Cu(2+), 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@Cu(2+) and 3@Cu(2+) 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.

Keywords: Cu(II) complex; Cytotoxicity; DNA cleavage; Dipyrrole-polyamide; Polyamine.