In vitro nephrotoxicity and anticancer potency of newly synthesized cadmium complexes

Sci Rep. 2019 Oct 11;9(1):14686. doi: 10.1038/s41598-019-51109-9.


Complexes based on heavy metals have great potential for the treatment of a wide variety of cancers but their use is often limited due to toxic side effects. Here we describe the synthesis of two new cadmium complexes using N(4)-phenyl-2-formylpyridine thiosemicarbazone (L1) and 5-aminotetrazole (L2) as organic ligands and the evaluation of their anti-cancer and nephrotoxic potential in vitro. The complexes were characterized by Single-crystal X-ray data diffraction, 1HNMR, FT-IR, LC/MS spectrometry and CHN elemental analysis. Next, cytotoxicity of these cadmium complexes was evaluated in several cancer cell lines, including MCF-7 (breast), Caco-2 (colorectal) and cisplatin-resistant A549 (lung) cancer cell lines, as well as in conditionally-immortalized renal proximal tubule epithelial cell lines for evaluating nephrotoxicity compared to cisplatin. We found that both compounds were toxic to the cancer cell lines in a cell-cycle dependent manner and induced caspase-mediated apoptosis and caspase-independent cell death. Nephrotoxicity of these compounds was compared to cisplatin, a known nephrotoxic drug, in vitro. Our results demonstrate that compound {2}, but not compound {1}, exerts increased cytotoxicity in MCF-7 and A549 cell lines, combined with reduced nephrotoxic potential compared to cisplatin. Together these data make compound {2} a likely candidate for further development in cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cadmium / chemistry
  • Cadmium / pharmacology*
  • Cell Cycle / drug effects
  • Cisplatin / adverse effects
  • Cisplatin / pharmacology
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Humans
  • Kidney / drug effects
  • Kidney / pathology
  • Ligands
  • MCF-7 Cells
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Spectroscopy, Fourier Transform Infrared
  • Tetrazoles / chemical synthesis
  • Tetrazoles / chemistry
  • Tetrazoles / pharmacology
  • Thiosemicarbazones / chemical synthesis
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / pharmacology


  • Antineoplastic Agents
  • Coordination Complexes
  • Ligands
  • Tetrazoles
  • Thiosemicarbazones
  • Cadmium
  • 5-amino-1H-tetrazole
  • Cisplatin