Han Bing-Jie, Jiang Guang-Bin, Yao Jun-Hua, Li Wei, Wang Ji, Huang Hong-Liang, Liu Yun-Jun
School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Spectrochim Acta A Mol Biomol Spectrosc. 2015 Jan 25;135:840-9. doi: 10.1016/j.saa.2014.07.075. Epub 2014 Aug 8.
Two new ruthenium(II) polypyridyl complexes Ru(dmb)2(dcdppz)2 (1) and Ru(bpy)2(dcdppz)2 (2) were prepared and characterized. The crystal structure of the complex 2 was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P21/n with a=12.9622(14)Å, b=17.1619(19)Å, c=22.7210(3)Å, β=100.930(2)(°), R=0.0536, Rω=0.1111. The DNA-binding constants for complexes 1 and 2 were determined to be 1.92×10(5) (s=1.72) and 2.24×10(5) (s=1.86)M(-1), respectively. The DNA-binding behaviors showed that complexes 1 and 2 interact with DNA by intercalative mode. The antioxidant activities of the ligand and the complexes were performed. Ligand, dcdppz, has no cytotoxicity against the selected cell lines. Complex 1 shows higher cytotoxicity than complex 2, but lower than cisplatin toward selected cell lines. The apoptosis and cell cycle arrest were investigated, and the apoptotic mechanism of BEL-7402 cells was studied by reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis. Complex 1 induces apoptosis in BEL-7402 cells through ROS-mediated mitochondrial dysfunction pathway and by regulating the expression of Bcl-2 family proteins.
制备并表征了两种新型钌(II)多吡啶配合物Ru(dmb)2(dcdppz)2(1)和Ru(bpy)2(dcdppz)2(2)。通过单晶X射线衍射解析了配合物2的晶体结构。该配合物结晶于单斜晶系,空间群为P21/n,a = 12.9622(14)Å,b = 17.1619(19)Å,c = 22.7210(3)Å,β = 100.930(2)(°),R = 0.0536,Rω = 0.1111。配合物1和2与DNA的结合常数分别测定为1.92×10(5)(s = 1.72)和2.24×10(5)(s = 1.86)M(-1)。DNA结合行为表明配合物1和2通过插入模式与DNA相互作用。进行了配体和配合物的抗氧化活性研究。配体dcdppz对所选细胞系无细胞毒性。配合物1对所选细胞系显示出比配合物2更高的细胞毒性,但低于顺铂。研究了凋亡和细胞周期阻滞,并通过活性氧(ROS)、线粒体膜电位和蛋白质印迹分析研究了BEL - 7402细胞的凋亡机制。配合物1通过ROS介导的线粒体功能障碍途径并通过调节Bcl - 2家族蛋白的表达诱导BEL - 7402细胞凋亡。