DNA binding, nuclease activity, DNA photocleavage and cytotoxic properties of Cu(II) complexes of N-substituted sulfonamides

Ternary copper(II) complexes [Cu(NST)2(phen)] (1) and [Cu(NST)2(NH3)2]·H2O (2) [HNST = N-(4,5-dimethylthiazol-2-yl)naphthalene-1-sulfonamide] were prepared and characterized by physico-chemical techniques. Both 1 and 2 were structurally characterized by X-ray crystallography. The crystal structures show the presence of a distorted square planar CuN4 geometry in which the deprotonated sulfonamide, acting as monodentate ligand, binds to the metal ion through the thiazole N atom. Both complexes present intermolecular π–π stacking interactions between phenanthroline rings (compound 1) and between naphthalene rings (compound 2). The interaction of the complexes with CT DNA was studied by means of thermal denaturation, viscosity measurements and fluorescence spectroscopy. The complexes display good binding propensity to the calf thymus DNA giving the order: 1 > 2. Complex 1, which has a higher capability for binding to DNA, showed better nuclease activity than 2 in the presence of ascorbate/H2O2. Both the kinetics and the mechanism of the DNA cleavage reaction were investigated. Furthermore, complex 1 showed efficient photo-induced DNA cleavage activity on irradiation with UV light in the absence of any external reagent. The UV light induced DNA cleavage follows a photo-redox pathway with generation of hydroxyl radicals as reactive species. In addition, the cytotoxic properties of both complexes (1 and 2) were evaluated in human cancer cells (HeLa, Caco-2 and MDA-468). The low IC50 values, in particular those against Caco-2, have indicated that the compounds can be considered as promising chemotherapeutic agents.

Graphical abstractTernary Cu(II)–sulfonamide complexes were prepared. Their DNA binding, nuclease activity, DNA photocleavage and cytotoxic properties were studied.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Two new Cu(II)-sulfonamide complexes were prepared and characterized. ► [Cu(NST)2(phen)] showed higher DNA binding propensity than [Cu(NST)2(NH3)2]·H2O. ► [Cu(NST)2(phen)] was able to cleave DNA on irradiation with UV light. ► The IC50 values indicated that the compounds could act as chemotherapeutic agents.