State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, Guangxi Normal University, 15 Yucai Road, Guilin, Guangxi 541004, China.
China Pharmaceutical University, Nanjing, Jiangsu, China.
Metallomics. 2019 Nov 1;11(11):1847-1863. doi: 10.1039/c9mt00193j. Epub 2019 Sep 25.
To develop new anti-tumour Pt(ii) agents, we designed and synthesized five Pt(ii) complexes. These Pt(ii) complexes were modified benzene rings of 2-hydroxybenzylidene with a hydrocarbyl or halogen group. The five Pt(ii) complexes possessed remarkable cytotoxicity against tumour cells in vitro. In particular, we investigated chemotherapeutic mechanisms of the complexes against A549cisR cells. The Pt(ii) complexes could bind to and cleave DNA, while also inducing arrest of the cell cycle in S phase, leading to down-regulation of the levels of cyclin-dependent kinases and cyclin and up-regulation of the expression of p21. The selected complex, C3, changed the mitochondrial membrane potential and induced apoptosis. C3 also inhibited the expression of the c-myc gene and downstream proteins, thereby inhibiting telomerase activity.
为了开发新的抗肿瘤铂(ii)配合物，我们设计并合成了五种铂(ii)配合物。这些铂(ii)配合物通过烃基或卤素基团对 2-羟基亚苄基苯环进行了修饰。五种铂(ii)配合物对体外肿瘤细胞具有显著的细胞毒性。特别是，我们研究了配合物对 A549cisR 细胞的化疗机制。铂(ii)配合物能够与 DNA 结合并使其断裂，同时诱导细胞周期在 S 期停滞，导致细胞周期蛋白依赖性激酶和细胞周期蛋白水平下调，p21 表达上调。所选的配合物 C3 改变了线粒体膜电位并诱导细胞凋亡。C3 还抑制了 c-myc 基因及其下游蛋白的表达，从而抑制了端粒酶的活性。
