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  

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

作　　者：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] 

机构地区：[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

出　　处：《有机化学》2011年第1期101-105,共5页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.20272046);湖北省自然科学基金(No.2006ABA227)资助项目

摘　　要：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。In this paper, 1-tosyl-3-hydroxyl-l,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.

关 键 词：大环多胺 断裂DNA 相互作用 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] O626[医药卫生—药学]