Synthesis, DNA binding and cleavage activity of macrocyclic polyamines bearing mono- or bis-acridine moieties

Two acridine-pendant cyclen (1,4,7,10-tetraazacyclododecane) derivatives 1 and 2 were synthesized, and their DNA interactions have been systematically investigated by UV absorption, fluorescence titration, viscosity measurement, DNA melting and gel electrophoresis experiments. The results showed that acridine-cyclen derivatives could bind to DNA in intercalative mode, and bis-acridine 2 has higher DNA binding ability than that of mono-acridine 1. Moreover, both compounds exhibited preferential interactions with G-rich DNA sequences. Their copper(II) complexes could cleave DNA without the existence of other additives under physiological conditions through an oxidative pathway.

Both of the acridine-pendant cyclen derivatives, especially 2, exhibited preferential binding to GC-rich DNA sequences. Their copper(II) complexes also showed effective DNA cleavage activities.Figure optionsDownload as PowerPoint slide