Redox-active copper(II) complexes with mixed heterocyclic N-donor ligands as dual antimicrobial and anti-tumor agents

A new series of complexes [Cu(N-N)₂(dmtp)](ClO₄)₂ (N-N = 2,2'-bipyridine (Cu1)/ 1,10-phenanthroline (Cu2) and dmtp = 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) was developed as biologically active species. The compounds were characterized using elemental analyses, IR, UV-Vis-NIR, EPR spectroscopy, electrochemistry, and single-crystal X-ray diffraction. Both complexes crystallize in the triclinic system, space group P-1, with two moieties in the unit cell. Both compounds exhibited varying antimicrobial efficacy, with (Cu2) demonstrating superior efficacy against Gram-positive bacteria and yeast strains. Complex (Cu2) also shows superior performance in inhibiting microbial adherence, which is crucial for preventing biofilm-related infections, particularly in the case of the E. coli strain. The study reveals that both complexes, at subinhibitory concentrations, increase intracellular nitric oxide levels, thereby inducing oxidative stress and protein oxidation, ultimately reducing microbial viability. In addition, the complexes exhibit selective superoxide-scavenging activity and interaction with DNA. In vitro cytocompatibility assays showed that compound (Cu1) induces apoptosis or cell cycle arrest in malignant melanoma (A375) and lung adenocarcinoma (A549), whereas compound (Cu2) induces necrosis, particularly at concentrations above 1 μM. The most potent effects were observed on lung adenocarcinoma cells. The docking data indicate that both complexes can interact with essential biomolecules involved in microbial pathogenesis and cancer progression.