Ru(III) complexes with pyrazolopyrimidines as anticancer agents: bioactivities and the underlying mechanisms

被引：22

作者：

Gu, Yun-Qiong ^{[1
,2
]}

Shen, Wen-Ying ^{[1
]}

Yang, Qi-Yuan ^{[1
]}

Chen, Zhen-Feng ^{[1
]}

Liang, Hong ^{[1
]}

机构：

[1] Guangxi Normal Univ, Sch Chem & Pharmaceut Sci, Collaborat Innovat Ctr Guangxi Ethn Med, State Key Lab Chem & Mol Engn Med Resources, Guilin 541004, Peoples R China

[2] Nanning Normal Univ, Sch Environm & Life Sci, Nanning 530001, Peoples R China

来源：

DALTON TRANSACTIONS | 2022年 / 51卷 / 04期

基金：

中国国家自然科学基金;

关键词：

G-QUADRUPLEX DNA; IN-VITRO; POLYPYRIDYL COMPLEXES; RUTHENIUM(II) COMPLEXES; BIOLOGICAL EVALUATION; INHIBITION; TELOMERASE; KINASE;

D O I：

10.1039/d1dt02765d

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(L-n)(H2O)Cl-3] (1-3, n = 1-3) were prepared and characterized. These Ru(III) compounds show strong cytotoxicity against six cancer cell lines and low toxicity to normal human liver cells. Particularly, they exhibited stronger cytotoxicity to SK-OV-3 cells than cisplatin. Mechanism studies revealed that complex 1 inhibited tumor cell invasion and suppressed cell proliferation, induced apoptosis by elevating the levels of intracellular ROS (reactive oxygen species) and free calcium (Ca2+), and reduced mitochondrial membrane potential (Delta Psi). It also activated the caspase cascade, accompanied with upregulation of cytochrome c, Bax, p53, Apaf-1 and downregulation of Bcl-2. Moreover, complex 1 caused cell cycle arrest at S phase by inhibiting the expression of CDC 25, cyclin A2 and CDK 2 proteins, and induced DNA damage by interacting with DNA and inhibiting the topoisomerase I enzyme. Complex 1 exhibited efficient in vivo anticancer activity in a model of SK-OV-3 tumor xenograft.

引用

页码：1333 / 1343

页数：12

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