Physicochemical properties and mechanism of action of a new copper(ii) pyrazine-based complex with high anticancer activity and selectivity towards cancer cells†

Two compounds, benzyl-2-(amino(pyrazin-2-yl)methylene)-1-methylhydrazine-1-carbodithioate (L) and its copper(II) complex Cu(L) were synthesized and studied in terms of their physicochemical properties, including single crystal, spectroscopic and magnetic properties; in silico simulations, including DFT calculations and pharmacokinetic profile analysis; and in vitro biological activity. The Cu(L) compound was found to exhibit good anticancer activity against A375, PANC-1, MKN-74, T-47D, HeLa, and NCI-H1563 cells, with the IC₅₀ value against the HeLa cell line reaching 17.50 μM, significantly surpassing the activity of the organic ligand. Moreover, at the same time, the Cu(L) complex did not exhibit significant toxicity towards healthy cells. Mechanism of action studies revealed that its activity is connected with the oxidative stress and redox imbalance caused by the upregulation of genes encoding superoxide dismutase (SOD2) and catalase (CAT) antioxidant enzymes. The reported results further underscore the anticancer potential of pyrazine-based copper(II) complexes.