Structural insights and in vitro and in vivo anticancer evaluation of dithiocarbamate-based metal complexes against murine lymphoma

Abstract

Metal-based chemotherapeutics have gained attention due to their ability to interfere with cellular functions. Dithiocarbamate ligands, known for their strong metal-binding properties, have been explored for their potential in anticancer applications. This study aims to synthesize and characterize dithiocarbamate-based Ni(ii), Cu(ii), and Zn(ii) complexes and evaluate their anticancer activity against Dalton's lymphoma (DL) cells. Three dithiocarbamate ligands (1-3) and their corresponding Ni(ii), Cu(ii), and Zn(ii) complexes (1a-c, 2a-c, and 3a-c) were synthesized and characterized using FT-IR, NMR, UV-Vis, and mass spectrometry, and single-crystal X-ray diffraction (SC-XRD). TGA analysis of complexes confirms their thermal stability up to 150 °C and the formation of metal sulfides at elevated temperatures. The in vitro antiproliferative activities of these compounds were assessed using the MTT assay. Apoptosis induction was analyzed via Annexin V-FITC/PI staining and flow cytometry. In vivo studies were conducted on a murine DL tumor model to evaluate therapeutic efficacy and biosafety. SC-XRD confirmed square planar geometries for Ni(ii) and Cu(ii) complexes, whereas Zn(ii) complexes exhibited a tetrahedral geometry. Metal complexes 1c, 2b, and 3c displayed the most potent antiproliferative activity, with 1c exhibiting the lowest IC<inf>50</inf> (7.1 μM). Apoptosis analysis indicated that 1c induced 64% apoptosis in DL cells. In vivo studies demonstrated that 1c significantly reduced tumor growth and prolonged survival, with minimal toxicity. The synthesized dithiocarbamate-metal complexes exhibited promising anticancer properties, particularly 1c, which demonstrated superior efficacy in both in vitro and in vivo models. These findings highlight the potential of metal-based dithiocarbamates as novel anticancer agents warranting further preclinical studies. © 2025 The Royal Society of Chemistry.