Gold Compounds as Anticancer Agents: Chemistry, Cellular Pharmacology, and Preclinical Studies
Gold Compounds as Anticancer Agents: Chemistry, Cellular Pharmacology, and Preclinical Studies
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DOI：
10.1002/med.20168
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发表时间：
2010-05-01
影响因子：
13.3
通讯作者：
Messori, Luigi
中科院分区：
文献类型：
--
作者：
Nobili, Stefania;Mini, Enrico;Messori, Luigi
金化合物是一类在癌症治疗方面具有巨大潜力的金属药物。在过去的二十年中，据报道，多种金（I）和金（III）化合物在体外对选定的人类肿瘤细胞系具有相关的抗增殖特性，使其成为进一步药理学评估的优秀候选者。金中心独特的化学性质赋予金基金属药物非常有趣和创新的药理学特征。本综述的主要目标是确定体外或体内进行的抗癌金化合物临床前研究的最新技术水平。详细分析了抗癌金化合物的现有研究，并特别关注潜在的分子机制。值得注意的是，一些生物物理学研究表明，细胞毒性金化合物与 DNA 的相互作用通常远弱于铂类药物，这意味着发生了截然不同的作用模式。因此提出了多种替代机制，其中涉及直接线粒体损伤或蛋白酶体抑制或特定激酶调节的机制现在受到高度认可。基于现有的实验证据，对开发具有创新作用机制的有效抗癌药物的金化合物的总体前景进行了批判性讨论。 © 2009 Wiley periodicals, Inc. Med Res Rev，30，第 3 期，550–580，2010 年
Gold compounds are a class of metallodrugs with great potential for cancer treatment. During the last two decades, a large variety of gold(I) and gold(III) compounds are reported to possess relevant antiproliferative properties in vitro against selected human tumor cell lines, qualifying themselves as excellent candidates for further pharmacological evaluation. The unique chemical properties of the gold center confer very interesting and innovative pharmacological profiles to gold‐based metallodrugs. The primary goal of this review is to define the state of the art of preclinical studies on anticancer gold compounds, carried out either in vitro or in vivo. The available investigations of anticancer gold compounds are analyzed in detail, and particular attention is devoted to underlying molecular mechanisms. Notably, a few biophysical studies reveal that the interactions of cytotoxic gold compounds with DNA are generally far weaker than those of platinum drugs, implying the occurrence of a substantially different mode of action. A variety of alternative mechanisms were thus proposed, of which those involving either direct mitochondrial damage or proteasome inhibition or modulation of specific kinases are now highly credited. The overall perspectives on the development of gold compounds as effective anticancer drugs with an innovative mechanism of action are critically discussed on the basis of the available experimental evidence. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 3, 550–580, 2010