Deo Krishant M, Pages Benjamin J, Ang Dale L, Gordon Christopher P, Aldrich-Wright Janice R
Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560, Australia.
School of Science and Health, Western Sydney University, Campbelltown, NSW 2560, Australia.
Int J Mol Sci. 2016 Oct 31;17(11):1818. doi: 10.3390/ijms17111818.
The diverse anticancer utility of cisplatin has stimulated significant interest in the development of additional platinum-based therapies, resulting in several analogues receiving clinical approval worldwide. However, due to structural and mechanistic similarities, the effectiveness of platinum-based therapies is countered by severe side-effects, narrow spectrum of activity and the development of resistance. Nonetheless, metal complexes offer unique characteristics and exceptional versatility, with the ability to alter their pharmacology through facile modifications of geometry and coordination number. This has prompted the search for metal-based complexes with distinctly different structural motifs and non-covalent modes of binding with a primary aim of circumventing current clinical limitations. This review discusses recent advances in platinum and other transition metal-based complexes with mechanisms of action involving intercalation. This mode of DNA binding is distinct from cisplatin and its derivatives. The metals focused on in this review include Pt, Ru and Cu along with examples of Au, Ni, Zn and Fe complexes; these complexes are capable of DNA intercalation and are highly biologically active.
顺铂多样的抗癌效用激发了人们对开发更多铂基疗法的浓厚兴趣，促使几种类似物在全球范围内获得临床批准。然而，由于结构和作用机制相似，铂基疗法的有效性受到严重副作用、活性谱狭窄以及耐药性发展的制约。尽管如此，金属配合物具有独特的特性和非凡的多功能性，能够通过轻松改变几何形状和配位数来改变其药理学性质。这促使人们寻找具有明显不同结构基序和非共价结合模式的金属基配合物，主要目的是规避当前的临床局限性。本综述讨论了铂基和其他过渡金属基配合物的最新进展，其作用机制涉及嵌入。这种DNA结合模式与顺铂及其衍生物不同。本综述重点关注的金属包括铂、钌和铜，以及金、镍、锌和铁配合物的例子；这些配合物能够嵌入DNA且具有高度生物活性。
