Structural insights andandanticancer evaluation of dithiocarbamate-based metal complexes against murine lymphoma.

in Dalton transactions (Cambridge, England : 2003) by Anupam Singh, Riya Patel, Samrat Daripa, M K Bharty, R J Butcher, Sumit Kumar Hira, Lal Bahadur Prasad

TLDR

  • The study synthesized and characterized dithiocarbamate-based Ni(II), Cu(II), and Zn(II) complexes and evaluated their anticancer activity against Dalton's lymphoma cells. The compound 1c displayed the most potent antiproliferative activity and significantly reduced tumor growth in a murine DL tumor model.
  • Key Insights: The study identified the most potent antiproliferative compound, assessed its therapeutic efficacy and biosafety, and highlighted the potential of metal-based dithiocarbamates as novel anticancer agents.

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. Theantiproliferative activities of these compounds were assessed using the MTT assay. Apoptosis induction was analyzedAnnexin V-FITC/PI staining and flow cytometry.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(7.1 μM). Apoptosis analysis indicated that 1c induced 64% apoptosis in DL cells.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 bothandmodels. These findings highlight the potential of metal-based dithiocarbamates as novel anticancer agents warranting further preclinical studies.

Overview

  • The 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.
  • The study employed various characterization techniques including FT-IR, NMR, UV-Vis, mass spectrometry, and single-crystal X-ray diffraction (SC-XRD) to analyze the complexes' structures and thermal stability.
  • The primary objective of the study is to identify the most potent antiproliferative compound and assess its therapeutic efficacy and biosafety in a murine DL tumor model.

Comparative Analysis & Findings

  • The study found that metal complexes 1c, 2b, and 3c displayed the most potent antiproliferative activity, with 1c exhibiting the lowest IC50 value (7.1 μM).
  • Apoptosis analysis indicated that 1c induced 64% apoptosis in DL cells, suggesting its potential as a cancer therapeutic.
  • The study demonstrated that 1c significantly reduced tumor growth and prolonged survival in a murine DL tumor model with minimal toxicity, making it a promising anticancer agent.

Implications and Future Directions

  • The study highlights the potential of metal-based dithiocarbamates as novel anticancer agents, warranting further preclinical studies to explore their efficacy and safety in various cancer types.
  • Future studies could focus on optimizing the synthesis and structural manipulation of these complexes to enhance their antiproliferative activity and targeting specificity.
  • The findings also suggest the possibility of designing metal-based compounds that can target specific cancer cells or pathways, reducing off-target effects and improving treatment outcomes.
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