Exploring biological properties of sulfa-based copper(II) complexes: in vitro genotoxicity, cytotoxicity (2D and 3D) and mechanistic insights

Given the need of more effective and safe treatments for diseases such as cancer, metal complexes can be highlighted. Among these, two copper(II) complexes linked to phenanthroline and two different sulfonamides identified as [Cu(smtr⁻)₂(phen)] (1) and [Cu(sdmx⁻)₂(phen)] (2) presented promising antibacterial and anti-proliferative activities. Continuing the in vitro preclinical studies, this study aimed to evaluate the cytotoxic effect on human colorectal tumor cells (HCT-15) and the genotoxic effect on immortalized Chinese hamster’s ovarian cells (CHO-K1) of complexes 1 and 2. Both complexes significantly reduced HCT-15 viability in monolayer and spheroid models, along with increased frequency of micronuclei after short-term treatment without metabolic activation in CHO-K1 cells. Furthermore, both in the presence of the metabolic enzyme mixture and with increasing exposure time, the genotoxic effect was not observed. In CHO-K1 cells, complexes 1 and 2 induced S-phase cycle arrest. Complex 2 was more active than complex 1 in increasing the production of reactive oxygen species in both cell lines evaluated. The cytotoxic and genotoxic effects observed for complexes 1 and 2 appear to be mediated by oxidative stress. Additional studies will be needed to further investigate the mechanisms of action, as well as to confirm the mutagenic potential of these complexes.