Department of Preclinical and Clinical Pharmacology, University of Florence, viale Pieraccini 6, 50139 Florence, Italy.
Med Res Rev. 2010 May;30(3):550-80. doi: 10.1002/med.20168.
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.
金化合物是一类具有巨大潜力的抗癌药物。在过去的二十年中，大量的金（I）和金（III）化合物被报道具有体外对选定的人类肿瘤细胞系的相关抗增殖特性，使它们成为进一步药理评价的优秀候选物。金中心的独特化学性质赋予基于金的金属药物非常有趣和创新的药理特性。这篇综述的主要目的是定义抗癌金化合物的临床前研究的最新进展，这些研究无论是在体外还是体内进行。对抗癌金化合物的现有研究进行了详细分析，并特别关注潜在的分子机制。值得注意的是，一些生物物理研究表明，细胞毒性金化合物与 DNA 的相互作用通常远弱于铂类药物，这意味着存在着一种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的调节的机制现在得到了高度认可。基于现有实验证据，本文批判性地讨论了将金化合物作为具有创新作用机制的有效抗癌药物的发展前景。
