Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, Belgrade 11,000, Serbia.
Faculty of Chemistry, University of Belgrade, Belgrade 11,000, Serbia.
Curr Med Chem. 2020;27(3):380-410. doi: 10.2174/0929867325666181031114306.
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 complexes.
To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms of action of metal complexes with various types of diamine ligands.
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.
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.
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.
顺铂的发现和随后的研究揭示了含二氮杂环部分对于金属配合物抗癌活性的重要性。此外，某些二胺配体本身具有细胞毒性，这有助于相应配合物的整体活性。
总结具有各种类型二胺配体的金属配合物的抗癌功效、选择性和作用机制的现有知识。
通过将脂环族无环、脂环族环状和芳族二胺配体与单独的有机配体和/或常规铂类化疗药物进行比较，分析它们对不同金属离子的金属配合物的抗癌活性和选择性/毒性的贡献。
脂环族无环二胺配体主要存在于铂配合物中。脂环族二胺是 Pt(II)、Ru(II) 和 Au(III) 配合物的一部分，而芳族二胺配体存在于 Pt(II)、Ru(II)、Pd(II) 和 Ir(III) 配合物中。金属离子的类型和氧化态极大地影响了具有脂环族无环二胺配体的金属配合物的细胞毒性。有机配体的亲脂性取决于烷基侧链的长度和结构，决定了它们的细胞摄取，其中 edda 和 eddp/eddip 配体最有用。脂环族二胺配体提高了奥沙利铂类配合物的活性/毒性比。具有芳族二胺配体的配合物在其抗癌机制方面仍未得到探索。所研究的配合物主要引起细胞凋亡或坏死性细胞死亡。
具有二胺配体的金属配合物是有前途的候选物，可作为高效且更具选择性的传统铂类化疗药物的替代品。需要进一步研究以揭示其生物活性的理化性质和分子机制。
