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癌症化疗中的点金术:从铂-到金-二硫代氨基甲酸盐配合物。

The Midas touch in cancer chemotherapy: from platinum- to gold-dithiocarbamato complexes.

机构信息

Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131, Padova, Italy.

出版信息

Dalton Trans. 2009 Dec 28(48):10670-80. doi: 10.1039/b913597a. Epub 2009 Sep 29.

Abstract

The unquestionable therapeutic success of the anticancer drug cisplatin and its second- and third-generation analogues has triggered, in the past forty years, the development of several metal-based potential chemotherapeutic agents, most of which have failed to enter clinical trials. In this context, during the last decade, our research group has been making quite an effort to design a number of metal-dithiocarbamato derivatives that were expected, at least in principle, to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Among all, gold(III) complexes have shown outstanding in vitro and in vivo antitumour properties and reduced or no systemic and renal toxicity, compared to the reference drug. Here, we summarize the results achieved to date, focusing on the mechanistic studies and the potential future developments opened up by our research work.

摘要

顺铂及其第二代和第三代类似物在抗癌药物方面的无可置疑的治疗成功,在过去的四十年中,引发了几种基于金属的潜在化疗药物的发展,其中大多数未能进入临床试验。在这种情况下,在过去的十年中,我们的研究小组一直在努力设计一系列金属-二硫代氨基甲酸盐衍生物,这些衍生物预计至少在原则上类似于顺铂的主要特征,同时具有更高的活性、更好的选择性和生物利用度,以及更低的副作用。在所有这些化合物中,与参比药物相比,三价金配合物表现出突出的体外和体内抗肿瘤特性,并且减少或没有全身和肾脏毒性。在这里,我们总结了迄今为止取得的结果,重点介绍了我们的研究工作所开展的机制研究和潜在的未来发展。

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