New heterobimetallic CuII–Sn2IV complex as potential topoisomerase I inhibitor: In vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines

The new heterobimetallic CuII–Sn2IV/NiII–Sn2IV complexes 1 and 2 bearing bioactive pharmacophore ligand scaffold; 1,10-phenanthroline and ethylenediamine were synthesized and characterized by spectroscopic (IR, UV–vis, NMR, ESI–MS) and analytical methods. The in vitro DNA binding studies of 1 and 2 with CT-DNA were carried out by employing various biophysical methods which reveal strong electrostatic binding via phosphate backbone of DNA helix, in addition to partial intercalation in the minor groove and stabilized by intramolecular hydrogen bonding. To gain further insight into the molecular recognition at the target site, UV–vis titrations of 1 with 5′-GMP was carried out and validated by 1H and 31P NMR. Complex 1 cleaved pBR322 DNA via oxidative pathway and exhibited high inhibition activity against Topo-I at 20 μM. Furthermore, the cytotoxicity of 1 was examined on a panel of human tumor cell lines of different histological origins showing promising antitumor activity.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New heterobimetallic complexes 1 and 2 were synthesized and characterized. ► DNA binding studies revealed dual mode of action at the molecular target site. ► Complex 1 cleaved pBR322 DNA via oxidative mechanism. ► Complex 1 showed high potential to act as an anticancer drug.