Synthesis, characterizations, and in vitro anticancer activity of di μ-acetato binuclear Zn(II) complexes with thiosemicarbazone ligands

Here, we report di μ-acetato bridged Zn(II) complexes {[Zn(μ-ac)CyHCT]₂ and [Zn(μ-ac)CyBHCT]₂} containing thiosemicarbazone alias hydrazine-1-carbothioamide ligands {N-Cyclohexyl-2-(1-(pyridin-2-yl)ethylidene)hydrazine-1-carbothioamide (HCyHCT) and N-Cyclohexyl-2-(phenyl(pyridin-2-yl)methylene)hydrazine-1-carbothioamide (HCyBHCT)}. The crystal structure of complexes shows that the Zn(II) centre is coordinated in a distorted trigonal bipyramidal configuration by three thiosemicarbazone atoms (two N and one S) and by an O atom from each of the two acetate groups. Further, di μ-acetato bridges in [Zn(μ-ac)CyBHCT]₂ are showing linkage isomerism. The ligand and complexes were further studied for their anticancer activities against the HT-29 (human colon) and DL (Dalton's lymphoma cells) cancer cells. The results imply that these compounds have superior cytotoxic activity against HT-29 cells. Additionally, among all the compounds [Zn(μ-ac)CyHCT]₂ has the most significant cytotoxic response with an IC₅₀ value close to 150 μM and 110 μM upon 24 h and 48 h incubation, respectively. Further assays DAPI staining, AO/EtBr dual staining, ROS production, and mitochondrial membrane potential measurement, were also performed to gain insights into the mechanism of cell death, and found that reduced and increased ROS production, highlighting mitochondrial-dependent apoptosis as the major mechanism for tumour cell death. In addition, the biocompatibility was further tested with HEK-293 (normal kidney) cells, which suggests the complex is biocompatible with a marginal cytotoxicity to normal cells.