Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Inorg Chem. 2013 Nov 4;52(21):12234-49. doi: 10.1021/ic400538c. Epub 2013 Jun 5.
Platinum compounds represent one of the great success stories of metals in medicine. Following the serendipitous discovery of the anticancer activity of cisplatin by Rosenberg, a large number of cisplatin variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. These efforts continue today with increased realization that new strategies are needed to overcome issues of toxicity and resistance inherent to treatment by the approved platinum anticancer agents. One approach has been the use of so-called "non-traditional" platinum(II) and platinum(IV) compounds that violate the structure-activity relationships that governed platinum drug-development research for many years. Another is the use of specialized drug-delivery strategies. Here we describe recent developments from our laboratory involving monofunctional platinum(II) complexes together with a historical account of the manner by which we came to investigate these compounds and their relationship to previously studied molecules. We also discuss work carried out using platinum(IV) prodrugs and the development of nanoconstructs designed to deliver them in vivo.
铂类化合物是金属在医学领域应用的重大成功范例之一。罗森伯格偶然发现顺铂具有抗癌活性后，人们制备了大量顺铂类似物，并对其杀伤癌细胞和抑制肿瘤生长的能力进行了测试。如今，人们越来越意识到，需要采用新的策略来克服已批准的铂类抗癌药物治疗中固有的毒性和耐药性问题。一种方法是使用所谓的“非传统”铂(II)和铂(IV)化合物，这些化合物违反了多年来指导铂类药物研发的结构-活性关系。另一种方法是使用专门的药物输送策略。在这里，我们描述了我们实验室最近的一些进展，涉及单功能铂(II)配合物，并回顾了我们研究这些化合物及其与先前研究分子关系的方式。我们还讨论了使用铂(IV)前药进行的工作以及设计用于体内递送它们的纳米结构的开发。
