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 IC₅₀ (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.