Targeting Nucleus DNA with a Cyclometalated Dipyridophenazineruthenium(II) Complex

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• 作者：Huaiyi Huang ; Pingyu Zhang ; Bole Yu ; Yu Chen ; Jinquan Wang ; Liangnian Ji ; Hui Chao
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：November 13, 2014
• 年：2014
• 卷：57
• 期：21
• 页码：8971-8983
• 全文大小：596K
• ISSN：1520-4804

文摘

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-魏B 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.