[1]雷春花,王雪玉,杨育才,等.小分子靶向受体酪氨酸激酶抑制剂TW9183的合成及体外抗肿瘤活性[J].华侨大学学报(自然科学版),2015,36(2):205-210.[doi:10.11830/ISSN.1000-5013.2015.02.0205]
 LEI Chun-hua,WANG Xue-yu,YANG Yu-cai,et al.Synthesis and Anti-Tumor Activities in Vitro of Small Molecule Targeted Receptor Tyrosine Kinase Inhibitor TW9183[J].Journal of Huaqiao University(Natural Science),2015,36(2):205-210.[doi:10.11830/ISSN.1000-5013.2015.02.0205]
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小分子靶向受体酪氨酸激酶抑制剂TW9183的合成及体外抗肿瘤活性()
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《华侨大学学报(自然科学版)》[ISSN:1000-5013/CN:35-1079/N]

卷:
第36卷
期数:
2015年第2期
页码:
205-210
栏目:
出版日期:
2015-03-20

文章信息/Info

Title:
Synthesis and Anti-Tumor Activities in Vitro of Small Molecule Targeted Receptor Tyrosine Kinase Inhibitor TW9183
文章编号:
1000-5013(2015)02-0205-06
作者:
雷春花1 王雪玉1 杨育才2 吴振3 王立强1
1. 华侨大学 生物医学学院, 福建 泉州 362021; 2. 台湾大学 生化科学系, 台湾 台北 106170; 3. 厦门大学 药学院, 福建 厦门 361101
Author(s):
LEI Chun-hua1 WANG Xue-yu1 YANG Yu-cai2 WU Zhen3 WANG Li-qiang1
1. School of Biomedical Sciences, Huaqiao University, Quanzhou 362021, China; 2. Department of Biochemical and Technology, National Taiwan University, Taibei 106170, China; 3. School of Pharmaceutical Sciences, Xiamen University, Xiamen 361101, China
关键词:
喹啉衍生物 受体酪氨酸激酶抑制剂 合成反应 抗肿瘤活性
Keywords:
quinoline derivatives receptor tyrosine kinase inhibitor synthesis reaction anti-tumor activity
分类号:
R916
DOI:
10.11830/ISSN.1000-5013.2015.02.0205
文献标志码:
A
摘要:
合成一系列喹啉类衍生物,初步筛选出候选药物TW9183,并对其体外抗肿瘤活性进行研究.4,7-二氯喹啉通过亲核取代、酰氯化及缩合反应得到TW9183.采用四甲基偶氮唑盐法(MTT)、平板克隆、划痕法、Hoechst 33342染色、蛋白免疫印迹及流式细胞术研究TW9183对3种人类肿瘤细胞(Hela,A549,SMMC-7721)的体外抑制作用.产物结构经红外光谱、核磁共振氢谱、碳谱、电喷雾质谱和元素分析表征确证.实验结果表明:TW9183能有效抑制3种肿瘤细胞的增殖,但对正常人脐静脉内皮细胞(HUVEC)无影响;Hoechst染色可见肿瘤细胞凋亡明显;TW9183能促进caspase-3活化形式的表达;划痕实验中肿瘤细胞迁移能力显著下降;流式细胞术表明其能将3种肿瘤细胞阻滞于G2/M期.
Abstract:
In this paper, a series of quinoline derivatives were synthesized. A lead compound, TW9183, was screened out preliminarily and investigated the anti-tumor activities in vitro. By nucleophilic substitution, acylchloride and condensation reaction, TW9183 could form from 4,7-dichloro quinoline. MTT plate cloning, scratching assay, Hoechst 33342 staining, western blot and flow cytometry were utilized to test the inhibitory effects of TW9183 against three types of human tumor cells(Hela,A549, and SMMC-7721)in vitro.The structure of the product was characterized by IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis. The results of assay showed that TW9183 could inhibit the proliferation of three types of tumor cells effectively, but have no effect on HUVEC; Hoechst 33342 staining revealed the obvious apoptosis of tumor cells; TW9183 could promote the expression of caspase-3 activation form; scratching assay suggested that the migration ability of tumor cells decreased dramatically; and flow cytometry detection demonstrated that cell cycle of tumor cells were arrested in the G2/M phase after treated with TW9183.

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备注/Memo

备注/Memo:
收稿日期: 2014-06-07
通信作者: 王立强(1970-),男,教授,博士,主要从事药剂学和新药开发的研究.E-mail:wlq1599@163.com.
基金项目: 福建省泉州市科技计划重点项目(2013Z35)
更新日期/Last Update: 2015-03-20