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下一代抗癌金属药物。

Next-generation anticancer metallodrugs.

机构信息

Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Japan. komedas@suzukau. ac.jp

出版信息

Curr Top Med Chem. 2012;12(3):219-35. doi: 10.2174/156802612799078964.

Abstract

More than 99% of currently approved clinical drugs are organic compounds. In contrast, the percentage of metal-containing drugs (metallodrugs) is very low. In cancer chemotherapy, however, platinum coordination compounds represented by cisplatin and derivatives thereof are essential anticancer agents with proven effects against a variety of tumors. Because of the proven clinical applications of these platinum-based drugs, the number of research initiatives to identify other metallodrugs that can be used for cancer therapy has increased considerably in the field of inorganic biochemistry. Anticancer platinum compounds continue to be designed and synthesized through several different approaches in order to improve the therapeutic effects and to overcome the disadvantages of current platinum-based drugs. The use of transition metal compounds other than platinum has also attracted attention. Gold coordination complexes, for instance, demonstrate outstanding cytotoxic properties, and certain ruthenium complexes possess a strong ability to inhibit metastases of solid invasive tumors. In this review, the potential of anticancer metallodrugs is described and representative examples from the most recent families of Pt-, Ru-, and Au-based compounds are discussed with respect to their possible modes of action and most probable biomolecular targets.

摘要

目前批准的临床药物中超过 99%为有机化合物。相比之下,含金属药物(金属药物)的比例非常低。然而,在癌症化疗中,以顺铂及其衍生物为代表的铂配合物是已被证明对多种肿瘤有效的基本抗癌药物。由于这些基于铂的药物的临床应用已得到证实,因此在无机生物化学领域中,已经有大量的研究计划旨在确定其他可用于癌症治疗的金属药物。为了提高治疗效果并克服当前基于铂的药物的缺点,人们继续通过几种不同的方法来设计和合成抗癌铂化合物。此外,人们还关注使用除铂以外的过渡金属化合物。例如,金配合物具有出色的细胞毒性,某些钌配合物具有强烈抑制实体侵袭性肿瘤转移的能力。在这篇综述中,描述了抗癌金属药物的潜力,并讨论了最近的铂、钌和金基化合物家族中的代表性实例,涉及它们可能的作用模式和最可能的生物分子靶标。

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