Design, synthesis and pharmacological evaluation of new 2-oxo-quinoline derivatives containing α-aminophosphonates as potential antitumor agents

被引：27
作者：
Yu, Yan-Cheng [1 ,2 ]
Kuang, Wen-Bin [2 ]
Huang, Ri-Zhen [2 ]
Fang, Yi-Lin [2 ]
Zhang, Ye [1 ,2 ,3 ]
Chen, Zhen-Feng [2 ]
Ma, Xian-Li [1 ]
机构：
[1] Guilin Med Univ, Coll Pharm, Guilin 541004, Peoples R China
[2] Guangxi Normal Univ, State Key Lab Chem & Mol Engn Med Resources, Minist Educ China, Sch Chem & Pharmaceut Sci, Guilin 541004, Peoples R China
[3] Guilin Normal Coll, Dept Chem & Pharmaceut Sci, Guilin 541001, Peoples R China
来源：
MEDCHEMCOMM | 2017年 / 8卷 / 06期
基金：
中国国家自然科学基金;
关键词：
ASIATIC ACID-DERIVATIVES; BREAST-CANCER CELLS; ANTICANCER AGENTS; APOPTOSIS; ANTIOXIDANT; MITOCHONDRIA; GROWTH; DEATH;
D O I：
10.1039/c7md00098g
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：
A series of novel 2-oxo-quinoline derivatives containing alpha-aminophosphonates were designed and synthesized as antitumor agents. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay results demonstrated that some compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3 and NCI-H460 tumor cell lines, and most compounds showed much lower cytotoxicity against HL-7702 normal cells than 5-FU and cisplatin. The action mechanism of representative compound 5b was investigated by fluorescence staining assay, flow cytometric analysis and western blot (WB) assay, which indicated that this compound induced apoptosis and G2/M phase arrest accompanied by an increase in the production of intracellular Ca2+ and reactive oxygen species (ROS) and affecting associated enzymes and genes.
引用
收藏
页码：1158 / 1172
页数：15
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