Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Dalton Trans. 2009 Dec 28(48):10651-9. doi: 10.1039/b913896j. Epub 2009 Oct 1.
The five platinum anticancer compounds currently in clinical use conform to structure-activity relationships formulated (M. J. Cleare and J. D. Hoeschele, Bioinorg. Chem., 1973, 2, 187-210) shortly after the discovery that cis-diamminedichloroplatinum(II), cisplatin, has antitumor activity in mice. These compounds are neutral platinum(II) species with two am(m)ine ligands or one bidentate chelating diamine and two additional ligands that can be replaced by water through aquation reactions. The resulting cations ultimately form bifunctional adducts on DNA. Information about the chemistry of these platinum compounds and correlations of their structures with anticancer activity have provided guidance for the design of novel anticancer drug candidates based on the proposed mechanisms of action. This article discusses advances in the synthesis and evaluation of such non-traditional platinum compounds, including cationic and tumor-targeting constructs.
目前有五种铂类抗癌化合物在临床上使用，它们符合在顺二氨二氯合铂(II)（cis-diamminedichloroplatinum(II)，cisplatin）被发现具有抗肿瘤活性后不久制定的结构-活性关系（M. J. Cleare 和 J. D. Hoeschele，Bioinorg. Chem.，1973，2，187-210）。这些化合物是中性铂(II)物种，具有两个氨（m）配体或一个双齿螯合二胺和两个额外的配体，可通过水合反应被水取代。由此产生的阳离子最终在 DNA 上形成双功能加合物。这些铂化合物的化学性质以及它们的结构与抗癌活性的相关性为基于拟议作用机制的新型抗癌药物候选物的设计提供了指导。本文讨论了此类非传统铂类化合物的合成和评估方面的进展，包括阳离子和肿瘤靶向构建体。
