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 the ligand structure, which plays a crucial role in therapeutic applications. In this context, two mononuclear homoleptic Cu(II) complexes, [Cu(L1 ) 2 ](ClO 4 ) 2 , 1 and[Cu(L2) 2 ](ClO 4 ) 2 , 2 (Where, L1 = 4-(2,6-di(pyrazin-2-yl)pyridin-4-yl)-N,N-dimethylaniline and L2 = 4-(2,6di(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 the Stern-Volmer constant (Ksv) were obtained in the range of 10 4 M -1 . Molecular docking studies were performed to gain knowledge about the interaction between B-DNA and the complexes. Furthermore, DNA nicking activity was monitored by in vitro electrophoresis analysis of supercoiled plasmid DNA. The effect of cell viability on MCF-7 and MDA-MB-231 cell lines was 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.