Structurally modified dipyrazinylpyridine-based homoleptic Cu(ii) complexes: comparative cytotoxic evaluation in breast cancer cell lines

Abstract

The DNA interaction ability of transition metal complexes is closely related to their ligand structure, which plays a crucial role in therapeutic applications. In this context, two mononuclear homoleptic Cu(II) complexes, [Cu(L1)₂](ClO₄)₂, 1, and [Cu(L2)₂](ClO₄)₂, 2 (where L1 = 4-(2,6-di(pyrazin-2-yl)pyridin-4-yl)-N,N-dimethylaniline and L2 = 4-(2,6-di(pyrazin-2-yl)pyridin-4-yl)-N,N-diphenylaniline), were synthesised and characterised using various spectroscopic and analytical techniques. SCXRD data indicate that in both complexes, the central Cu(II) unit is oriented in a distorted octahedral manner. The redox performance of the complexes was investigated using various voltammetric techniques. The DNA-binding ability of the complex was investigated using absorbance spectroscopy and ethidium bromide (EB) fluorescence quenching studies with double-stranded salmon sperm DNA (ss-DNA). The binding constant (K_b) and Stern–Volmer constant (K_sv) were obtained in the range of 10⁴ M⁻¹. Molecular docking studies were performed to understand the interactions between B-DNA and the complexes. Furthermore, DNA nicking activity was monitored by in vitro electrophoresis analysis of the supercoiled plasmid DNA. The effects of cell viability on MCF-7 and MDA-MB-231 cell lines were investigated. Cellular production of reactive oxygen species (ROS) was determined using a fluorescent probe (Calcein-AM). Notably, co-administration of 1 with Camptothecin (CPT) enhanced the overall cytotoxic effect, suggesting a synergistic therapeutic response. Interestingly, these results could lead to the development of cost-effective non-platinum transition metal-based chemotherapeutic agents to overcome the lacuna of the present conventional drugs.