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Curr Med Chem. 2018 Oct 31. doi: 10.2174/0929867325666181031114306. [Epub ahead of print]

Current Development of Metal Complexes with Diamine Ligands as Potential Anticancer Agents.

Author information

1
School of Medicine University of Belgrade - Institute of Medical and Clinical Biochemistry Belgrade. Serbia.
2
Faculty of Chemistry University of Belgrade Belgrade. Serbia.
3
School of Medicine University of Belgrade - Institute of Microbiology and Immunology Belgrade. Serbia.

Abstract

BACKGROUND:

The discovery of cisplatin, and the subsequent research, revealed the importance of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain diamine ligands alone display the cytotoxicity that contributes to overall activity of corresponding complexes.

OBJECTIVE:

To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.

METHOD:

The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the anticancer activity and selectivity/toxicity of metal complexes with different metal ions was analyzed by comparison with organic ligand alone and/or conventional platinum-based chemoterapeutics.

RESULTS:

The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic diamine ligands remain unexplored regarding anticancer mechanism. The investigated complexes mainly caused apoptotic or necrotic cell death.

CONCLUSION:

Metal complexes with diamine ligands are promising candidates for efficient and more selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.

KEYWORDS:

anticancer; diamine ligand; in vitro; in vivo; metal complex; toxicity

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