State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
Curr Opin Chem Biol. 2014 Apr;19:144-53. doi: 10.1016/j.cbpa.2014.02.003. Epub 2014 Mar 5.
Since the discovery of the cisplatin antitumor activity, great efforts have focused on the rational design of metal-based anticancer agents that can be potentially used in cancer chemotherapy. Over the last four decades, a large number of metal complexes have been extensively investigated and evaluated in vitro and in vivo, and some of them were at different stages of clinical studies. Amongst these complexes, platinum (Pt(II) and Pt(IV)), ruthenium (Ru(II) and Ru(III)), gold (Au(I) and Au(III)) and titanium (Ti(IV)) complexes are the most studied metals. We describe here some most recent progresses on Pt(IV) prodrugs which can be activated once enter tumor cells, polynuclear Pt(II) complexes which have unique DNA binding ability and mode, anti-metastatic Ru(II)/Ru(III) complexes, and Au(I)/Au(III) and Ti(IV) antitumor active complexes. The key focuses of these studies lie in finding novel metal complexes which could potentially overcome the hurdles of current clinical drugs including toxicity, resistance and other pharmacological deficiencies.
自从发现顺铂的抗肿瘤活性以来,人们已经做出了巨大的努力,致力于设计合理的基于金属的抗癌药物,这些药物有可能用于癌症化疗。在过去的四十年中,已经对大量的金属配合物进行了广泛的体外和体内研究和评估,其中一些已经处于不同的临床研究阶段。在这些配合物中,铂(Pt(II) 和 Pt(IV))、钌(Ru(II) 和 Ru(III))、金(Au(I) 和 Au(III))和钛(Ti(IV))配合物是研究最多的金属。我们在这里描述了一些最近在 Pt(IV)前药方面的进展,这些前药一旦进入肿瘤细胞就可以被激活,具有独特的 DNA 结合能力和模式的多核 Pt(II)配合物,抗转移 Ru(II)/Ru(III)配合物,以及具有抗肿瘤活性的 Au(I)/Au(III)和 Ti(IV)配合物。这些研究的重点在于寻找新的金属配合物,这些配合物有可能克服当前临床药物包括毒性、耐药性和其他药理学缺陷等方面的障碍。