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Imine‐N‐Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p‐Cymene Anticancer Complexes: A Structure–Activity Relationship Study
Chemistry - An Asian Journal ( IF 4.1 ) Pub Date : 2018-09-05 , DOI: 10.1002/asia.201801058
Yuliang Yang 1 , Lihua Guo 1 , Zhenzhen Tian 1 , Xicheng Liu 1 , Yuteng Gong 1 , Hongmei Zheng 1 , Xingxing Ge 1 , Zhe Liu 1
Affiliation  

A family of novel imine‐N‐heterocyclic carbene ruthenium(II) complexes of the general formula [(η6p‐cymene)Ru(C^N)Cl]PF6 (where C^N is an imine‐N‐heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine‐N‐heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD+ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complex 9 shows the highest anticancer activity in this series against A549 cancer cells (IC50=14.36 μm), with an approximately 1.5‐fold better activity than the clinical platinum drug cisplatin (IC50=21.30 μm) in A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.

中文翻译:

亚胺-N-杂环卡宾作为钌(II)对-Cymene抗癌复合物中的多功能配体:结构-活性关系研究

通式[(η的新颖亚胺N-杂环卡宾钌(II)配合物的家族6 - p PF的Ru(C ^ N)氯-cymene)] 6 - (其中,C ^ N是亚胺甲基-N-已经制备并表征了具有不同取代基的杂环卡宾螯合配体。在这种亚胺-N-杂环卡宾螯合配体框架中,可以修饰三个潜在位点,从而区分了这类配体,并提供了一定的灵活性和机会来调节这些钌(II)配合物的细胞毒性。三个可调结构域的取代基效应对辅酶NADH转化为NAD +的抗癌活性和催化能力的影响被调查。尽管它们的结构相似,但该复合物家族对A549癌细胞显示出极其不同的抗癌活性。复杂 9示出了在这一系列对A549癌细胞最高抗癌活性(IC 50 = 14.36μ),具有约1.5倍的临床铂药物顺铂(IC更好的活性50 = 21.30μ在A549癌细胞)。机理研究表明,复杂 9介导细胞死亡的主要途径是通过细胞应激,包括细胞周期停滞,诱导细胞凋亡,增加细胞内活性氧(ROS)水平以及线粒体膜电位(MMP)的去极化。此外,还通过共聚焦显微镜检测到了溶酶体损伤。
更新日期:2018-09-05
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