Department of Life Sciences, University of Trieste, via L. Giorgieri 7, 34127 Trieste, Italy.
Dalton Trans. 2012 Jul 21;41(27):8226-34. doi: 10.1039/c2dt30075c. Epub 2012 May 22.
The development of metal-based anticancer drugs is mainly governed by the experience accumulated with cisplatin and its analogues. The synthesis is focused on adding appropriate leaving and non-leaving groups to a transition metal in order to get more favorable DNA binding properties, and the biological activity is tested in vitro, always in a second step, looking for the cell line that is killed at the lowest drug concentration. This strategy seems unproductive today for the area of new drug development where the knowledge on cancer genomics is suggesting the use of targets selectively expressed, or overexpressed by cancer cells. These targets almost always are proteins, constituting membrane receptors or components of crucial biochemical pathways. Some data indicate that the antitumor activity of cisplatin might also be due to the interaction with protein targets. This critical review examines the possibilities for metal-based drugs to challenge tumors with innovative strategies, based on genomic approaches, capitalizing on the chemical experiences with metals in medicine and focusing on the nature of the ligands which are added to a metal depending on the selected tumor cells and on their molecular targets.
金属抗癌药物的发展主要取决于顺铂及其类似物积累的经验。合成的重点是在过渡金属上添加适当的离去和非离去基团，以获得更有利的 DNA 结合特性，并在体外测试生物活性，总是在第二步，寻找在最低药物浓度下被杀死的细胞系。对于新药开发领域来说，这种策略似乎没有成效，因为癌症基因组学的知识表明，应该使用选择性表达或过度表达的靶标。这些靶标几乎总是蛋白质，构成膜受体或关键生化途径的组成部分。一些数据表明，顺铂的抗肿瘤活性也可能是由于与蛋白质靶标的相互作用。这篇评论性文章考察了基于基因组方法的金属药物用创新策略来对抗肿瘤的可能性，利用金属在医学中的化学经验，并根据选定的肿瘤细胞及其分子靶标，关注添加到金属上的配体的性质。
