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Synthesis and structure of new binuclear ruthenium(ii) arene benzil bis(benzoylhydrazone) complexes: investigation on antiproliferative activity and apoptosis induction†
Inorganic Chemistry Frontiers ( IF 6.1 ) Pub Date : 2017-12-26 00:00:00 , DOI: 10.1039/c7qi00761b
Mohamed Subarkhan Mohamed Kasim 1, 2, 3, 4, 5 , Saranya Sundar 1, 2, 3, 4, 5 , Ramesh Rengan 1, 2, 3, 4, 5
Affiliation  

A series of binuclear ruthenium(II) arene benzil bis(benzoylhydrazone) complexes (1–6) of the common composition [(η6-arene)2Ru2(L)Cl2] (arene = benzene or p-cymene; L = benzil bis(benzoylhydrazone derivatives)) have been synthesized. The synthesised complexes have been thoroughly characterised by elemental analysis, IR, NMR, UV-vis and ESI-MS spectral methods. The coordination of the binucleating ligand to each ruthenium centre through azomethine nitrogen and imidolate oxygen was confirmed by single crystal XRD, which indicates the presence of the pseudo octahedral geometry. All the complexes were carefully screened for their cytotoxicity against HeLa, MDA-MB-231 and Hep G2 cells under in vitro conditions. Interestingly, the complexes 4 and 6 exhibit higher cytotoxicity than cisplatin, with low IC50 values against all screened cancer cell lines. Furthermore, the mode of cell death in MDA-MB-231 cells was assessed by AO-EB, Hoechst 33258 staining and a flow cytometry technique along with the comet assay. The result of western blot analysis suggests that complexes 4 and 6 were shown to induce apoptosis via the mitochondrial pathway by up-regulating p53 and Bax, and down-regulating Bcl-2.

中文翻译:

新型双核钌(ii)芳烃苄基双(苯甲酰hydr)配合物的合成和结构:抗增殖活性和凋亡诱导的研究

一系列双核钌(的II)芳烃苯偶酰二(苯甲酰)复合物(1-6)的组合物共同[(η 6 -arene)2的Ru 2(L)氯2 ](芳烃=苯或p-cymene; L =苯甲双(苯甲酰hydr衍生物)。合成的配合物已通过元素分析,IR,NMR,UV-vis和ESI-MS光谱法进行了全面表征。通过单晶XRD证实了双核配体通过偶氮甲碱氮和亚氨氧基氧与每个钌中心的配位,表明存在伪八面体几何形状。在体外条件下仔细筛选所有复合物对HeLa,MDA-MB-231和Hep G2细胞的细胞毒性。有趣的是,配合物46具有比顺铂更高的细胞毒性,且IC 50对所有筛选的癌细胞系的评估值。此外,通过AO-EB,Hoechst 33258染色和流式细胞仪技术以及彗星测定法评估了MDA-MB-231细胞中的细胞死亡方式。蛋白质印迹分析的结果表明,复合物46通过上调p53和Bax和下调Bcl-2通过线粒体途径诱导凋亡。
更新日期:2017-12-26
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