MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University , Guangzhou, 510275, China.
J Med Chem. 2014 Nov 13;57(21):8971-83. doi: 10.1021/jm501095r. Epub 2014 Oct 23.
Recently, coordinatively saturated and substitutionally inert Ru(II) complexes have been investigated as anticancer agents. Herein a cyclometalated Ru(II) complex, Ru(bpy)(phpy)(dppz), was found to be rapidly taken up by cancer cells, and nearly 90% of the complex accumulated in the nuclei of cancer cells after a 2 h incubation. The anticancer activity of this complex was screened against a panel of cancer cell lines. Remarkably, it exhibited IC50 values that were an order of magnitude lower than those of cisplatin. This complex also displayed potencies superior to those of cisplatin against 3D tumor spheroids. Further studies revealed that the high DNA binding affinity of Ru(bpy)(phpy)(dppz) resulted in effective disruption of the binding of transcription factor NF-κB to DNA sequences, thereby inhibiting cellular transcription and leading to irreversible cancer cell apoptosis. Our work provides new insights into understanding the biological interactions and anticancer molecular mechanisms of DNA-specific Ru(II) polypyridyl complexes.
最近，配位饱和且取代惰性的 Ru(II) 配合物被研究作为抗癌剂。本文中，一种环金属化的 Ru(II) 配合物 [Ru(bpy)(phpy)(dppz)] (+) 被发现能够被癌细胞快速摄取，并且在孵育 2 小时后，几乎 90%的配合物积累在癌细胞的核内。该配合物的抗癌活性在一组癌细胞系中进行了筛选。值得注意的是，它表现出的 IC50 值比顺铂低一个数量级。该配合物对 3D 肿瘤球体的效力也优于顺铂。进一步的研究表明，[Ru(bpy)(phpy)(dppz)] (+) 与 DNA 的高结合亲和力导致转录因子 NF-κB 与 DNA 序列结合的有效破坏，从而抑制细胞转录并导致不可逆的癌细胞凋亡。我们的工作为理解 DNA 特异性 Ru(II) 多吡啶配合物的生物相互作用和抗癌分子机制提供了新的见解。
