Structure - activity relationships of 2-quinolinecarboxaldehyde thiosemicarbazone gallium(III) complexes with potent and selective anticancer activity

被引：36

作者：

Cao, Wanbao ^{[1
]}

Qi, Jinxu ^{[1
]}

Qian, Kun ^{[1
]}

Tian, Liang ^{[1
]}

Cheng, Zhen ^{[2
]}

Wang, Yihong ^{[1
]}

机构：

[1] Southeast Univ, Sch Chem & Chem Engn, Nanjing 211189, Jiangsu, Peoples R China

[2] Stanford Univ, Stanford Canc Inst, Acad Council, Stanford, CA 94305 USA

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2019年 / 191卷

基金：

中国国家自然科学基金;

关键词：

2-Quinolinecarboxaldehyde thiosemicarbazone; Gallium(III) complex; Anticancer activity; Metallodrugs; CELLULAR UPTAKE; ANTIPROLIFERATIVE ACTIVITY; ANTITUMOR-ACTIVITY; CANCER-CELLS; APOPTOSIS; DI-2-PYRIDYLKETONE; EXPRESSION; INDUCTION; CASPASE-3; GA(III);

D O I：

10.1016/j.jinorgbio.2018.11.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Six gallium(III) complexes (Gal-Ga6) with 2-quinolinecarboxaldehyde thiosemicarbazone analogues were synthesized and characterized. These gallium(III) complexes exhibited potent anticancer activity and exceeded that of the corresponding metal free ligands. Importantly, these gallium(III) complexes have a strong selectivity for tumor cells. Through the study of cellular mechanisms, we have found that the lipophilicity of ligands is closely linked to the antitumor activity of gallium(III) complexes. Additionally, we have chosen Ga6 with the best anti-tumor activity to study the mechanism of apoptosis. Caspase-3 and 9 activation and Annexin V-FITC/Propidium iodide (PI) dual-staining studies revealed that Ga6 promote apoptosis in A549 cells lines. Ga6 induces intracellular reactive oxygen species (ROS) and disrupts mitochondrial membrane potential.

引用

页码：174 / 182

页数：9

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