State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, P.R. China.
Anticancer Agents Med Chem. 2010 Jun;10(5):396-411. doi: 10.2174/1871520611009050396.
Platinum-based anticancer chemotherapy constitutes a cornerstone for the treatment of various solid tumors. However, existing platinum drugs like cisplatin encounter many obstacles such as drug resistance and systemic toxicity in clinical applications. Extensive attempts have been made to minimize the side effects of platinum drugs. This review concentrates on the major development of novel platinum complexes in the last five years, and highlights the complexes with DNA damage mode fundamentally different from that of cisplatin. Diverse platinum complexes are discussed in the text, including analogues of cisplatin or oxaliplatin, monofunctional platinum(II) complexes, polynuclear platinum(II) complexes, trans-platinum(II) complexes, and platinum(IV) complexes. All of these complexes display impressive antitumor activity and some of them show remarkable potentiality to circumvent the resistance to cisplatin. On the basis of these new facts, it can be concluded that structural modifications could substantially modulate the DNA binding mode and DNA damage process, and as a result largely improve the antitumor efficacy of platinum complexes.
基于铂的抗癌化疗是治疗各种实体瘤的基石。然而，现有的铂类药物（如顺铂）在临床应用中遇到了许多障碍，如耐药性和全身毒性。人们已经进行了广泛的尝试来最小化铂类药物的副作用。本综述集中讨论了过去五年中新型铂配合物的主要发展，并强调了与顺铂的 DNA 损伤模式根本不同的配合物。文中讨论了多种铂配合物，包括顺铂或奥沙利铂的类似物、单功能铂（II）配合物、多核铂（II）配合物、反式铂（II）配合物和铂（IV）配合物。所有这些配合物都表现出令人印象深刻的抗肿瘤活性，其中一些配合物显示出显著的潜力，可以规避顺铂的耐药性。基于这些新事实，可以得出结论，结构修饰可以显著调节 DNA 结合模式和 DNA 损伤过程，从而大大提高铂类配合物的抗肿瘤疗效。
