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Rigid dinuclear ruthenium-arene complexes showing strong DNA interactions
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2018-08-24 , DOI: 10.1016/j.jinorgbio.2018.08.013
Qi Wu , Liu-Yi Liu , Shunli Li , Fang-Xin Wang , Ji Li , Yong Qian , Zhi Su , Zong-Wan Mao , Peter J. Sadler , Hong-Ke Liu

Six novel dinuclear Ru(II)-arene complexes [Ru2(η6-p-cymene)2(1,3-bib)2Cl22·Solvent (X = Cl (1), I (2), NO3 (3), BF4 (4), PF6 (5), CF3SO3 (6); 1,3-bib = 1,3-di(1H-imidazol-1-yl) benzene) were synthesized and fully characterized by FT-IR, 1H NMR, ESI-MS, Elemental Analysis (EA) and Powder X-ray Diffraction (PXRD). Single crystal X-ray diffractions studies showed that 3 and 4 have rigid bowl-like structures, where one counter-anion (NO3 for 3 and BF4 for 4) was trapped inside the cavity to balance the charge, respectively. Even complexes 16 showed only moderate or little anti-proliferative activity toward cancer cells, strong interactions with DNA molecules through intercalation, however, were confirmed by UV-Vis, CD and fluorescence spectroscopy. Apoptosis and cell cycle arrest studies for complex 2 with cancer A549 cells indicated concentration-dependent late apoptosis and the G1/G0 phase arrest. Interactions with the tripeptide glutathione (γ-L-Glu-L-Cys-Gly, GSH) might explain the relatively low antiproliferative potency of these complexes. This class of rigid dinuclear cations hold potential as DNA-targeting anticancer agents if their uptake and delivery could be under controlled.



中文翻译:

刚性双核钌-芳烃复合物显示出强大的DNA相互作用

六米新颖的双核钌(II)配合物-arene的[Ru 2η 6 - p -cymene)2(1,3-围兜222 ·溶剂(X =氯- 1),I - 2),NO 3 - 3),BF 4 - 4),PF 6 - 5),CF 3 SO 3 - 6); 1,3-围兜 合成了1,3-二(1H-咪唑-1-基)苯并通过FT-IR,1 H NMR,ESI-MS,元素分析(EA)和粉末X射线衍射(PXRD)进行了全面表征。单晶X射线衍射研究表明,34具有刚性盆状结构,其中,一个反阴离子(NO 3 -3和BF 4 -4)被困在腔内部分别以平衡电荷。甚至是复合物16展示了对癌细胞仅中等或极小的抗增殖活性,通过嵌入与DNA分子发生了强相互作用,但是,通过UV-Vis,CD和荧光光谱证实了这一点。对具有癌A549细胞的复合物2的凋亡和细胞周期阻滞研究表明,浓度依赖性的晚期细胞凋亡和G1 / G0期阻滞。与三肽谷胱甘肽(γ-L-Glu-L-Cys-Gly,GSH)的相互作用可能解释了这些复合物相对较低的抗增殖能力。如果可以控制其摄取和释放,这类刚性双核阳离子具有作为靶向DNA的抗癌剂的潜力。

更新日期:2018-08-24
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