Future of toxicology-iron chelators and differing modes of action and toxicity: The changing face of iron chelation therapy
Future of toxicology-iron chelators and differing modes of action and toxicity: The changing face of iron chelation therapy
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DOI：
10.1021/tx700039c
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发表时间：
2007-05-01
影响因子：
4.1
通讯作者：
Richardson, Des R.
中科院分区：
文献类型：
--
作者：
Kalinowski, Danuta S.;Richardson, Des R.
铁（Fe）螯合疗法最初是为了减轻铁超载疾病中过量Fe的毒性作用。然而，一些铁螯合剂-金属配合物的新的毒理学性质已经将可感知的焦点转移到它们在癌症化疗中的应用上。无氧化还原活性的Fe螯合剂络合物非常适合于治疗Fe超负荷疾病，而具有高氧化还原活性的Fe螯合剂络合物已显示出作为抗癌化疗剂的有希望的结果。在这个角度来看，我们讨论了不同的作用模式和毒理学概况的铁螯合剂，包括类似物的2-吡啶基甲醛异烟酰腙，二-2-吡啶基酮异烟酰腙，二-2-吡啶基酮氨基硫脲，和临床试验螯合剂3-氨基吡啶-2-甲醛氨基硫脲。这些药物的潜在应用在改变铁螯合治疗的面貌进行了讨论。
Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted appreciable focus to their application in cancer chemotherapy. Redox-inactive Fe chelator complexes are well suited for the treatment of Fe-overload diseases, whereas Fe chelator complexes with high redox activity have shown promising results as chemotherapeutics against cancer. Within this perspective, we discuss the different modes of action and toxicological profiles of Fe chelators, including analogues of 2-pyridylcarboxaldehyde isonicotinoyl hydrazone, di-2-pyridylketone isonicotinoyl hydrazone, di-2-pyridylketone thiosemicarbazone, and the clinically trialed chelator 3-aminopyridine-2-carboxaldehyde thiosemicarbazone. The potential application of these agents in the changing face of Fe chelation therapy is discussed.