Piperazine-Based Co(III), Ni(II), Cu(II), and Zn(II) Carbodithioate Complexes as Potential Anticancer Agent

The development of facile and cost-effective anticancer metallodrugs possessing minimal side effects is urgently needed. Piperazine-containing anticancer drugs are already available on the market. A piperazine-based potassium 4-(ethoxycarbonyl)piperazine-1-carbodithioate [pecpcdt] (<b>L</b>) ligand and its metal complexes [Co(ecpcdt)₃] (<b>1</b>), [Ni(ecpcdt)₂] (<b>2</b>), [Cu(ecpcdt)₂] (<b>3</b>), and [Zn(ecpcdt)₂] (<b>4</b>) were synthesized. These compounds were characterized by different spectroscopic methods and single-crystal X-ray crystallography data. Ni(II) and Cu(II) complexes have distorted square planar geometry, whereas the Co(III) complex has distorted octahedral geometry around the metal ions. Complexes are weakly fluorescent in the solution compared to the free ligand. The complexes were further examined for their <i>in vitro</i> anticancer activities against the primary Dalton's lymphoma (DL) cells along with standard drug cisplatin. The anticancer studies of metal complexes have been performed through various biochemical assays, and the findings thus obtained suggest that they demonstrate an effective anticancer activity. [Co(ecpcdt)₃] (<b>1</b>) shows superior cytotoxicity against DL cells than complexes [Cu(ecpcdt)₂] (<b>3</b>), [Zn(ecpcdt)₂] (<b>4</b>), and cisplatin. The superiority preferences of these complexes follows [Co(ecpcdt)₃] (<b>1</b>) > [pecpcdt] > [Cu(ecpcdt)₂] (<b>3</b>) > [Ni(ecpcdt)₂] (<b>2</b>) > [Zn(ecpcdt)₂] (<b>4</b>). Further assays were performed on a cobalt(III) complex having the highest efficacy to gain insights into the mechanism of cell death and showed that reduced mitochondrial membrane potential and increased mitochondrial ROS production, highlighting mitochondrial-dependent apoptosis as the major mechanism for tumor cell death. On the other hand, the viability of normal splenocytes was minimally affected by the [Co(ecpcdt)₃] (<b>1</b>) treatment.