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 cytotoxicity that contributes to the overall activity of corresponding
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.
Methods: 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 were analyzed
by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.
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 their 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.