Synthesis, characterization, and cytotoxic properties of mono- and di-nuclear cobalt(II)-polypyridyl complexes

被引：23

作者：

Eskandari, Arvin ^{[1
]}

Kundu, Arunangshu ^{[2
]}

Lu, Chunxin ^{[3
]}

Ghosh, Sushobhan ^{[2
]}

Suntharalingam, Kogularamanan ^{[1
]}

机构：

[1] Kings Coll London, Dept Chem, London, England

[2] Gauhati Univ, Dept Chem, Gauhati, India

[3] Qinzhou Univ, Guangxi Coll & Univ Key Lab Beibu Gulf Oil & Nat, Qinzhou 535011, Peoples R China

来源：

DALTON TRANSACTIONS | 2018年 / 47卷 / 16期

关键词：

COBALT-ALKYNE COMPLEXES; CANCER-THERAPY; BIOLOGICAL EVALUATION; ANTICANCER AGENTS; CRYSTAL-STRUCTURE; ARSENIC TRIOXIDE; ANTITUMOR DRUGS; METAL-COMPLEXES; HISTONE H2AX; DNA-DAMAGE;

D O I：

10.1039/c8dt00577j

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

We report the synthesis and characterisation of mono- and di-nuclear cobalt(ii) complexes (1-3) containing L-1, a polypyridyl ligand with pyrazole moieties. DNA binding studies suggest that the mono-nuclear complex, 1, binds to DNA via the grooves prior to inducing oxidative DNA cleavage whereas the larger di-nuclear complexes, 2 and 3, bind to DNA via the grooves and through intercalation prior to inducing oxidative DNA cleavage. The cobalt(ii) complexes display micromolar potency towards U2OS (bone osteosarcoma), HepG2 (liver hepatocellular carcinoma), and GM05757 (normal human fibroblast) cells, comparable to clinically used platinum agents, cisplatin and carboplatin. The cellular mechanism of action studies show that the most effective cobalt(ii) complex, 2, enters U2OS cells, penetrates the nucleus, induces genomic DNA damage, and triggers caspase-dependent apoptosis in a p53-independent manner. This study highlights the potential of di-nuclear cobalt(ii) complexes as artificial oxidative metallonucleases and tangible cancer cell-potent agents.

引用

页码：5755 / 5763

页数：9

共 55 条

[11] Biological evaluation of non-steroidal anti-inflammatory drugs-cobalt(II) complexes [J].