高等学校化学学报 ›› 2004, Vol. 25 ›› Issue (3): 470.

• 研究论文 • 上一篇    下一篇

含羟基环多胺金属配合体系切割DNA及其体外抗肿瘤活性研究

梁峰1, 魏俊2, 李朝阳2, 吴成泰1, 郑从义2, 孙蒙祥2   

  1. 1. 武汉大学化学系;
    2. 武汉大学生命科学学院, 武汉 430072
  • 收稿日期:2003-03-07 出版日期:2004-03-24 发布日期:2004-03-24
  • 通讯作者: 吴成泰(1937年出生),男,教授,博士生导师,主要从事大环化学研究.E-mail;chemoliangf@yahoo.com.cn E-mail:chemoliangf@yahoo.com.cn
  • 基金资助:

    国家自然科学基金(批准号;29972034)资助

Hydroxyl Macrocyclic Polyamines Coordination Systems Interaction with DNA and Their Antitumor Activities in vitro

LIANG Feng1, WEI Jun2, LI Zhao-Yang2, WU Cheng-Tai1, ZHENG Cong-Yi2, SUN Meng-Xiang2   

  1. 1. Department of Chemistry;
    2. School of Life Sciences, Wuhan University, Wuhan 430072, China
  • Received:2003-03-07 Online:2004-03-24 Published:2004-03-24

摘要: 研究了3-羟基-1,5,8-三氮杂环癸烷(L1)和3,13-二羟基-1,5,8,11,15,18-六氮杂二十元环胺(L2)与Ni(Ⅱ),Ca(Ⅱ),Co(Ⅱ),Cu(Ⅱ)离子在不同配比下与质粒pBR322DNA及肝癌细胞BEL-7402的相互作用情况.发现L1的单核体系和L2的双核体系能有效地将超螺旋DNA同时切割得到切口开环型和线型DNA,并对BEL-7402表现出明显的生长抑制作用.

关键词: 大环多胺, DNA切割, 抗肿瘤活性

Abstract: The interaction between plasmid DNA (pBR322 DNA) and Ni(Ⅱ), Ca(Ⅱ), Co(Ⅱ), Cu(Ⅱ) coordination systems of 3-hydroxyl-1,5,8-triaazacyclic amine (L1) and 3,13-dihydroxyl-1,5,8,11,15,18-hexaazacyclic amine (L2) with several molar ratios were investigated by agarose gel electrophoresis. The results suggested that M L1, M L2 and 2M L2 systems could catalyze the cleavage of supercoiled pBR322 DNA to the nicked and the linear form at the same time under near neutral conditions at 37 ℃. The efficiency of DNA cleavage decreased in the order 2M-L2>M-L2, because there was probably cooperativity between two metal ions in 2M-L2 systems which catalyzed the cleavage of DNA. The little cleavage was found under a comparable conditions by the metal ions or receptor alone. The antitumor activities of two receptors, metal ions and their metal coordination systems were all measured against BEL 7402 cell lines by using MTT assay. The metal ions have cytotoxicity to cells at 10-3mol/L ; but when it was diluted to 10-4mol/L, the percentage inhibition decreased sharply. On the contrary, the metal coordination systems still kept their antitumor activities even at 10-5mol/L. Thus, these coordination systems may be useful as artificial restriction enzymes and may be usefully applied to the development of antitumor drug.

Key words: Macrocyclic polyamines, DNA cleavage, Antitumor activity

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