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

Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(L )(H O)Cl ] (1-3, = 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-...

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Published in:Dalton transactions : an international journal of inorganic chemistry 2022-01, Vol.51 (4), p.1333-1343
Main Authors: Gu, Yun-Qiong, Shen, Wen-Ying, Yang, Qi-Yuan, Chen, Zhen-Feng, Liang, Hong
Format: Article
Language:English
Subjects:
Anticancer properties
Apoptosis
Biocompatibility
Calcium ions
Cancer
Cell cycle
Cytochromes
Cytotoxicity
Pyrazolopyrimidines
Ruthenium
Toxicity
Tumors
Xenotransplantation
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Summary:Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(L )(H O)Cl ] (1-3, = 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 (Ca ), and reduced mitochondrial membrane potential (Δ ). It also activated the caspase cascade, accompanied with upregulation of cytochrome , 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 anticancer activity in a model of SK-OV-3 tumor xenograft.
ISSN:1477-9226
1477-9234
DOI:10.1039/d1dt02765d