Wang Lijun, Zheng Chuping, Liu Yanyu, Le Fangling, Yang Fang, Qin Xiuying, Wang Chuan, Liu Jie
College of Chemistry and Biology, Beihua University, Jilin, 132013, People's Republic of China.
Biol Trace Elem Res. 2014 Feb;157(2):175-82. doi: 10.1007/s12011-013-9869-3. Epub 2014 Jan 11.
A new Ru(II)-Se complex, Ru(bpy)2L2Cl2 (bpy = 2,2'-bipyridine, L = 1,10-phenanthrolineselenazole) (Ru-Se) has been synthesized and characterized. The G-quadruplex DNA-binding properties of the complex and its selenium ligand (Phen-Se) were evaluated by thermal denaturation study, polymerase chain reaction (PCR) stop assay, and telomerase repeat amplification protocol (TRAP). The results showed that the obtained complex could induce and stabilize G-quadruplex structure as well as exhibit potent inhibitory activity against telomerase. In vitro cytotoxicity studies showed that complex Ru-Se inhibited the cancer cell growth through apoptosis. However, the presence of the ligand Phen-Se did not appear to have a significant effect either on G-quadruplex binding or on biological activity. Furthermore, the cell migration assay and the tube formation assay also demonstrated that the complex Ru-Se significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration, and tube formation. These findings indicate that the Ru-Se complex may be a potential telomerase inhibitor and a viable drug candidate in antiangiogenesis for anticancer therapies.
一种新型的钌（II）-硒配合物Ru(bpy)2L2Cl2（bpy = 2,2'-联吡啶，L = 1,10-菲咯啉硒唑）（Ru-Se）已被合成并表征。通过热变性研究、聚合酶链反应（PCR）终止试验和端粒酶重复序列扩增法（TRAP）评估了该配合物及其硒配体（Phen-Se）与G-四链体DNA的结合特性。结果表明，所获得的配合物能够诱导并稳定G-四链体结构，同时对端粒酶表现出强大的抑制活性。体外细胞毒性研究表明，配合物Ru-Se通过凋亡抑制癌细胞生长。然而，配体Phen-Se的存在似乎对G-四链体结合或生物活性均无显著影响。此外，细胞迁移试验和成管试验还表明，配合物Ru-Se显著抑制人脐静脉血管内皮细胞（HUVEC）的增殖、迁移和成管。这些发现表明，Ru-Se配合物可能是一种潜在的端粒酶抑制剂，也是抗癌治疗中抗血管生成的一种可行候选药物。
