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有机化学
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有机化学 ›› 2011, Vol. 31 ›› Issue (01): 101-105. 上一篇    下一篇

研究论文

1-对甲苯磺酰基-3-羟基-1,5,8-三氮杂环癸烷的合成及与DNA的相互作用研究

李涛1，吴晓军2，梁峰*,2，熊小琴2，杨利2，周泱泱2，吴成泰2   

  1. (1华中科技大学同济医学院附属同济医院眼科 武汉 430030)
    (2武汉大学化学与分子科学学院 武汉 430072)
  • 收稿日期:2010-05-26 修回日期:2010-09-27 发布日期:2010-10-10
  • 通讯作者: 李涛 E-mail:dr_litao@163.com

Synthesis of 1-Tosyl-3-hydroxyl-1,5,8-triazacyclodecane and Its In-teraction with DNA

Li Tao1 Wu Xiaojun2 Liang Feng*,2 Xiong Xiaoqin2 Yang Li2 Zhou Yangy-ang2 Wu Chengtai2   

  1. (1 Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030)
    (2 College of Chemistry & Molecular Sciences, Wuhan University, Wuhan 430072)
  • Received:2010-05-26 Revised:2010-09-27 Published:2010-10-10

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1259

被引次数

12 | 1

通过控制反应条件, 制备得到1-对甲苯磺酰基-3-羟基-1,5,8-三氮杂环癸烷(2). 根据谱学数据确定目标化合物2的结构, 应用DNA熔点温度测量和计算机模拟研究测定化合物2～4与DNA的结合能力. 结果显示羟基和对甲苯磺酰基的引入有利于化合物2与DNA的结合. 在37 ℃生理条件作用下, 不需要金属离子辅助, 大环配体2可使超螺旋型pBR322 DNA断裂, 同时得到切口开环型和线形DNA. 并且, 化合物2对肺癌细胞有选择性抑制作用. 因此, 这种先导化合物可以用于人工核酸酶及抗肿瘤药物设计.

关键词: 大环多胺, 断裂DNA, 相互作用, 抗肿瘤活性

In this paper, 1-tosyl-3-hydroxyl-1,5,8-triazacyclodecane (2) was prepared in optimized conditions. The structure of title compound 2 was established on the basis of spectroscopic data. The binding of compounds 2, 3, 4 to DNA was investigated with melting temperature measurements and molecular-modeling calculations. The results showed that the introduction of hydroxyl and tosyl groups into triazacyclicamines may enhance the interaction between the compound 2 and DNA. The free macrocyclic ligand 2 could catalyze cleavage supercoiled pBR322 DNA to the nicked and the linear form at the same time at near neutral conditions and 37 ℃ without any metal ions aid. In addition, compound 2 showed selectively inhibition to lung cancer cells. Thus, this leading compound might be useful as artificial restriction enzymes and may be usefully applied in the development of anti-tumor drug.

Key words: macrocyclic polyamines, DNA cleavage, interaction, antitumor activity