Marzano Cristina, Pellei Maura, Tisato Francesco, Santini Carlo
Dipartimento di Scienze Farmaceutiche, Università di Padova, Padova, Italy.
Anticancer Agents Med Chem. 2009 Feb;9(2):185-211. doi: 10.2174/187152009787313837.
Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field.
金属基抗肿瘤药物在抗恶性肿瘤化疗中发挥着重要作用。顺铂被认为是最有效的药物之一，尽管严重的毒性和耐药现象限制了其临床应用。因此，近年来新型金属基抗癌药物的研发迅速扩展，以提高临床疗效、降低总体毒性并拓宽活性谱。生物学中金属离子功能的多样性刺激了除铂类药物之外的新型金属药物的开发，目的是获得通过替代作用机制发挥作用的化合物。在非铂类化合物中，铜配合物作为抗癌剂具有潜在吸引力。实际上，多年来许多研究基于内源性金属可能毒性较小的假设积极研究铜化合物。已经确定，铜配位化合物的性质在很大程度上取决于与金属离子结合的配体和供体原子的性质。在本综述中，讨论了作为抗肿瘤剂的铜（I、II）配合物设计和开发方面最显著的成就。特别强调了不同类别的铜（I、II）配合物构效关系的确定。这项工作的动机是观察到文献中没有关于铜配合物作为抗癌剂的全面综述。此外，到目前为止，尽管在合成不同类别的铜配合物方面付出了巨大努力，但关于其抗肿瘤活性潜在机制的分子基础的数据却非常少。本综述收集了过去十年中为设计有前景的抗癌铜（I、II）化合物所采用的最重要策略，将对该领域的研究人员有所帮助。
