A multifunctional molecular entity CuII–SnIV heterobimetallic complex as a potential cancer chemotherapeutic agent: DNA binding/cleavage, SOD mimetic, topoisomerase Iα inhibitory and in vitro cytotoxic activities

New chiral L-valine-derived Schiff base complexes with the bioactive heterocyclic ligand scaffold pyrazole (Hpz) were designed and synthesized with a view to find their potential as anticancer chemotherapeutic drug candidates. The monometallic chemical entities CuII (1) and ZnII (2), and heterobimetallic CuII–SnIV (3), and ZnII–SnIV (4) were synthesized and characterized adopting various spectroscopic (UV-vis, IR, 1H 13C and 119Sn NMR, EPR and ESI-MS) and analytical methods. In vitro, CT-DNA-binding profiles of 1–4 were studied by UV-vis, fluorescence spectroscopy, and circular dichroism. The results display the significantly higher binding affinity of heterobimetallic complexes 3 and 4 than monometallic complexes 1 and 2. This could be attributed to the dual binding mode facilitating a preferential electrostatic interaction via SnIV towards the surface phosphate oxygen of the sugar–phosphate backbone of the DNA double helix, in addition to the covalent overlap of CuII to N7 of the guanine of the DNA. Moreover, complex 3 exhibited significantly efficient DNA cleavage activity involving the formation of the superoxide radical as well as the hydroxyl radical as the reactive species. The SOD-like activity of 3 and 4 was evaluated using a xanthine/xanthine oxidase assay, which showed SOD activity in the micromolar range for both the heterobimetallic complexes viz., (IC50) 0.082 μM for 3 and 12 μM for 4. Furthermore, 3 showed high inhibitory activity against Topo-Iα at a concentration of 20 μM as IC50, suggesting that complex 3 is an efficient DNA cleaving agent. In vitro studies on the anticancer activity against the HepG2 hepatocellular carcinoma cell line revealed that both complexes 3 and 4 have the capability to kill the chosen cancer cell, but the efficiency of complex 3 is 10 times higher than 4. The mode of cell death induced by complex 3 is primarily apoptosis as revealed by AO/EB staining, Hoechst 33258 staining, and assessment of the mitochondrial trans-membrane potential.