Novel tetranuclear ruthenium(II) arene complexes showing potent cytotoxic and antimetastatic activity as well as low toxicity in vivo

被引：149

作者：

Subarkhan, Mohamed Kasim Mohamed ^{[1
]}

Ren, Lulu ^{[2
]}

Xie, Binbin ^{[2
]}

Chen, Chao ^{[3
]}

Wang, Yuchen ^{[1
]}

Wang, Hangxiang ^{[1
]}

机构：

[1] Zhejiang Univ, Key Lab Combined Multiorgan Transplantat, Affiliated Hosp 1, Minist Publ Hlth,Sch Med, Hangzhou 310003, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Med Oncol, Hangzhou 310016, Zhejiang, Peoples R China

[3] Huzhou Univ, Coll Life Sci, Huzhou 313000, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 179卷

基金：

中国国家自然科学基金;

关键词：

Tetranuclear Ru(II) arene complexes; In vitro cytotoxicity; Apoptosis; Antimetastasis; Drug toxicity; ANTIPROLIFERATIVE ACTIVITY; POLYMERIC NANOPARTICLES; DERIVATIVES SYNTHESIS; ANTICANCER COMPLEXES; APOPTOSIS; DELIVERY; VITRO; CHEMISTRY; LIGAND;

D O I：

10.1016/j.ejmech.2019.06.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Ruthenium complexes have attracted a surge of interest as anticancer drug candidates because of their low toxicity, diversity in mode-of-actions and non-cross drug resistance with conventional platinum-based agents. Despite remarkable advances, only a limited number of ruthenium complexes have been demonstrated to kill cancer cells and suppress metastasis simultaneously. Here, two organometallic tetranuclear Ru(II) arene complexes (Ru-1 and Ru-2) have been synthesized and evaluated for their in vitro activity against a panel of human cancer cell lines, including a cisplatin-resistant human lung cancer A549 cell line. A superior cytotoxic activity of the ruthenium complexes compared to cisplatin across distinct cell lines was observed. Further examination of the mechanism indicated that anticancer activity was accomplished by inducing apoptosis in cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Importantly, choosing Ru-1 as a target compound, a significantly enhanced safety profile relative to cisplatin in animals was validated, suggesting that these complexes can be used as promising candidates for cancer therapy and deserve further investigation. (C) 2019 Elsevier Masson SAS. All rights reserved.

引用

页码：246 / 256

页数：11

共 56 条

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