Sullivan Matthew P, Holtkamp Hannah U, Hartinger Christian G
Met Ions Life Sci. 2018 Feb 5;18. doi: 10.1515/9783110470734-019.
Anticancer platinum-based drugs are widely used in the treatment of a variety of tumorigenic diseases. They have been identified to target DNA and thereby induce apoptosis in cancer cells. Their reactivity to biomolecules other than DNA has often been associated with side effects that many cancer patients experience during chemotherapy. The development of metal compounds that target proteins rather than DNA has the potential to overcome or at least reduce the disadvantages of commonly used chemotherapeutics. Many exciting new metal complexes with novel modes of action have been reported and their anticancer activity was linked to selective protein interaction that may lead to improved accumulation in the tumor, higher selectivity and/or enhanced antiproliferative efficacy. The development of new lead structures requires bioanalytical methods to confirm the hypothesized modes of action or identify new, previously unexplored biological targets and pathways. We have selected original developments for review in this chapter and highlighted compounds on track toward clinical application.
基于铂的抗癌药物广泛应用于多种致瘤性疾病的治疗。它们已被确定可靶向DNA，从而诱导癌细胞凋亡。它们对DNA以外生物分子的反应性常常与许多癌症患者在化疗期间经历的副作用相关。开发靶向蛋白质而非DNA的金属化合物有可能克服或至少减少常用化疗药物的缺点。已经报道了许多具有新颖作用模式的令人兴奋的新型金属配合物，它们的抗癌活性与选择性蛋白质相互作用有关，这可能导致在肿瘤中的积累增加、更高的选择性和/或增强的抗增殖功效。新先导结构的开发需要生物分析方法来确认假设的作用模式或识别新的、以前未探索的生物靶点和途径。在本章中，我们选择了一些原创进展进行综述，并重点介绍了有望进入临床应用的化合物。
