Telomere DNA Binding, Cleavage and Anticancer Activity of [Cu(phendione)(Hpyramol)Cl]

Abstract

Background:The ligand Hpyramol is a redox active, which on coordination with Cu(II) cleaves DNA without any added reductant. Another ligand phendione is known for its wide application towards anticancer activities. We combined the ligands with CuCl2 to have an intercalation moiety and a redox active ligand in participation towards telomere DNA cleavage and anticancer activity.Objective:In this study, our aim is to interact it with Human telomere DNA and to see their effects on cancer cells.Methods:The complex [Cu(L)(L’)Cl] has interacted with the human telomere DNA sequence (TTAGGG), HTelo20. The HTelo20 was stabilized under both parallel and antiparallel G-quadruplex conformations and the complex [Cu(L)(L’)Cl] has interacted followed by circular dichroism spectroscopy and gel electrophoresis.Results:The parallel G-quadruplex and randomly coiled conformations of HTelo20 were easily cleaved than the anti-parallel G-quadruplex conformation. The nature of DNA cleavage was found to be oxidative rather hydrolytic. The formation of phenoxyl radical species under electrochemical and controlled potential electrolysis conditions by the complex [Cu(L)(L’)Cl] proves the possibility of oxidative nature of DNA cleavage. The comet assay also proves the DNA cleavage induced by the complex [Cu(L)(L’)Cl] inside the nucleus of HeLa cancer cells.Conclusion:The complex [Cu(L)(L’)Cl] was tested for anticancer activity, induced by ROS and DNA cleavage. The IC50 values resulted in nanomolar concentrations with selected cancer cell lines. Relatively the Cu complex shows less toxicity with the normal cell line L132.