Sun Jing, Chen Wen-Xiu, Song Xing-Dong, He Shu-Fen, Chen Jia-Xi, Mei Jun, Zhu Xiao-Xian, Wu Tie
School of Pharmacy, Guangdong Medical University, Dongguan, 523808, China.
Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, 524023, China.
Anticancer Agents Med Chem. 2018;18(1):110-120. doi: 10.2174/1871520617666170419122056.
Two new ruthenium(II) complexes containing guanidinium as ligands, [Ru(dip)2 (L1)]3+ (Ru1) and [Ru(dip)2(L2)]3+ (Ru2) (dip=4,7-diphenyl-1,10-phenanthroline; L1=1-(4-(1H-imidazo[4,5- f][1,10]phenanthrolin-2-yl)phenyl)guanidine cation; L2 = 1-(3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl) phenyl)guanidine cation) have been synthesized and characterized. Both complexes display higher cytotoxicity against several cancer cell lines compared to cisplatin and are less cytotoxic on the nontumorigenic cell line LO2. Intracellular distribution studies show that these complexes are selectively localized in the cytoplasm.
Further analysis revealed that Ru1 and Ru2 had no obvious effects on the cell cycle and induced apoptosis in HeLa cells via the mitochondrial pathway, which involved reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and Bcl-2 family member activation. Taken together, the two complexes have the potential to be utilized as anticancer agents.
合成并表征了两种以胍盐为配体的新型钌（II）配合物，[Ru(dip)2 (L1)]3+（Ru1）和[Ru(dip)2(L2)]3+（Ru2）（dip = 4,7 - 二苯基 - 1,10 - 菲咯啉；L1 = 1 - (4 - (1H - 咪唑并[4,5 - f][1,10]菲咯啉 - 2 - 基)苯基)胍阳离子；L2 = 1 - (3 - (1H - 咪唑并[4,5 - f][1,10]菲咯啉 - 2 - 基)苯基)胍阳离子）。与顺铂相比，这两种配合物对几种癌细胞系均表现出更高的细胞毒性，而对非致瘤细胞系LO2的细胞毒性较小。细胞内分布研究表明，这些配合物选择性地定位于细胞质中。
进一步分析表明，Ru1和Ru2对细胞周期无明显影响，并通过线粒体途径诱导HeLa细胞凋亡，这涉及活性氧（ROS）积累、线粒体功能障碍和Bcl - 2家族成员激活。综上所述，这两种配合物有潜力用作抗癌剂。
