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端粒酶在肿瘤细胞中高表达,已经成为抗肿瘤药物的重要靶点,由于很多肿瘤细胞中富含G4-DNA,通过稳定G-四链体DNA的形成来抑制端粒酶的活性已成为抗癌药物的一个新策略.本文设计了两种钌配合物,调查了这两种钌配合物稳定G4-DNA的能力,发现配合物2稳定端粒G4-DNA的能力强于配合物1,配合物2能够诱导端粒G4-DNA发生构型的转化,而配合物1不能诱导G4-DNA发生构型的转化,这项研究结果证明,钌配合物与G4-DNA的作用能力与配体的平面性有关.在抗肿瘤活性方面,配合物2表现出更强的抗肿瘤活性,尤其是对HepG2细胞具有较强的抑制作用,推测其是以端粒酶为靶点发挥的抗肿瘤作用.配合物2能够诱导肿瘤细胞凋亡,能诱导G1期细胞阻滞和DNA碎片的形成(细胞凋亡的特征).据此推测本论文设计的钌配合物是一个潜在的抗肿瘤药物.
The high expression of telomerase in tumor cells has become an important target of anticancer drugs. Since many tumor cells are rich in G4-DNA, telomerase activity has been turned down by stabilizing G-quadruplex DNA formation Cancer drugs.This paper designed two ruthenium complexes and investigated the ability of the two ruthenium complexes to stabilize G4-DNA and found that the ability of complex 2 to stabilize telomeric G4-DNA is stronger than that of complex 1, Substance 2 can induce the transformation of the telomeric G4-DNA conformation, while complex 1 can not induce the transformation of G4-DNA conformation. The results of this study demonstrate that the ability of the ruthenium complex to interact with G4- In the aspect of anti-tumor activity, complex 2 showed stronger anti-tumor activity, especially HepG2 cells, which was presumed to be an antitumor effect targeting telomerase. Complex 2 can induce tumor cell apoptosis, induce cell arrest in G1 phase and form DNA fragmentation (apoptosis characteristics), suggesting that the designed ruthenium complex in this thesis is a potential anti-tumor drug.