A series of homoleptic bis(terpyridine)copper(II) complexes of the type [Cu(L^1–5)₂]Cl₂ (1–5), where L^1–5 = 4′-(4-substituted)-2,2′:6′,2′′-terpyridines, have been synthesized and characterized. The molecular structure of complex 2 was confirmed by the single crystal XRD technique, and the geometry of the complexes is best described as distorted octahedral. Structural parameters from the crystallographic and DFT studies are in good agreement with each other. The small HOMO–LUMO energy gap supports bioefficacy of the complexes. DNA binding studies show high intrinsic binding constant values 1.53 ± 0.15, 1.62 ± 0.08 and 3.09 ± 0.12 × 10⁵ M⁻¹ for complexes 1, 2 and 3, respectively, with intercalative mode of binding to CT-DNA. The binding results were further supported by molecular docking studies. The experimental results indicate that the interaction between the complexes and BSA protein involves a static quenching mechanism. The molecular docking studies with c-Met tyrosine kinase receptors show hydrophobic and π–π interactions. All the complexes bring about hydroxyl radical mediated DNA cleavage in the presence of H₂O₂. In vitro cytotoxicities of the complexes (1–3) were tested against three cancerous cell lines, namely human breast adenocarcinoma (MCF-7), epithelioma (Hep-2) and cervical (HeLa) cell lines, and one non-tumorigenic human dermal fibroblast (NHDF) cell line by MTT reduction assay. The morphological assessment data obtained using Hoechst 33258 staining revealed that complex 3 induces apoptosis much more effectively than the other complexes.

A series of six new bis(thiosemicarbazone)copper(I) complexes of the type [Cu(L^1–6)₂Cl] (1–6) have been synthesized and characterized. The molecular structure of the ligand L⁴ was determined by the single crystal XRD method. All the complexes adopted trigonal planar (Y-shaped) geometry. All the complexes strongly bind with CT-DNA via intercalative mode, which was further supported by molecular docking studies. Further, the complexes were effectively bind with BSA as observed by UV-Vis and fluorescence spectra. All the complexes effectively cleave pBR322 DNA through hydrolytic pathway as evidenced from T4 ligase experiments. All the complexes interact with the anticancer receptor focal adhesion kinase (FAK) via electrostatic, van der Waals, hydrogen bonding, σ–π and π–π interactions. In vitro cytotoxicity of the complexes were assessed by MTT assay against four cancer cell lines such as human breast adenocarcinoma (MCF-7), cervical (HeLa), epithelioma (Hep-2) and Ehrlich ascites carcinoma (EAC), and two normal cell lines namely normal human dermal fibroblasts (NHDF) and L6 myotubes with respect to the commercially used anticancer drug cisplatin. All the complexes induce apoptosis in EAC cells, which was confirmed by AO/EB, Hoechst 33258 and PI staining methods. The complexes block cell cycle progression of EAC cells in S phase (DNA synthesis). The cellular uptake studies confirmed the ability of the complexes to go into the cytoplasm and accumulation in the cell nuclei. In the in vivo anticancer studies, the complexes significantly reduce the tumour volume in female Swiss albino mice. Overall, our results ensure the role of thiosemicarbazone-based copper(I) complexes as prospective anticancer agents, induction of apoptosis and S phase arrest with the mitochondrial controlled pathway.