高等学校化学学报

高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (05): 976.doi: 10.3969/j.issn.0251-0790.2012.05.020

• 有机化学 • 上一篇    下一篇

1,2,5-硒二唑嘧啶衍生物ASPO的合成及抗氧化与抗肿瘤活性

黄晓纯1, 郑军生2, 陈填烽1, 张逸波1, 罗懿1, 郑文杰1   

  1. 1. 暨南大学化学系, 广州 510632;
    2. 中山大学附属第三医院, 广州 510630
  • 收稿日期:2011-06-20 出版日期:2012-05-10 发布日期:2012-05-10
  • 作者简介:陈填烽, 男, 博士, 教授, 博士生导师, 主要从事化学靶向药物设计与药效学研究. E-mail: tchentf@jnu.edu.cn
  • 基金资助:

    教育部新世纪优秀人才支持计划(批准号: NCET 10-0119), 国家自然科学基金(批准号: 20901030, 21071062)和广东省科技攻关项目(批准号: 2008A030201020)资助.

Synthesis, Antioxidant and Anticancer Activities of 1,2,5-Selenadiazole Pyrimidine Heterocyclic Derivative ASPO

HUANG Xiao-Chun1, ZHENG Jun-Sheng2, CHEN Tian-Feng1, ZHANG Yi-Bo1, LUO Yi1, ZHENG Wen-Jie1   

  1. 1. Department of Chemistry, Jinan University, Guangzhou 510632, China;
    2. The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
  • Received:2011-06-20 Online:2012-05-10 Published:2012-05-10

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被引次数

10

摘要： 合成了5-氨基-[1,2,5]硒二唑[3,4-d]嘧啶-7-酮(ASPO), 研究了其抗氧化与抗肿瘤活性, 并初步阐述了其作用机制. 结果表明, ASPO具有良好的抗氧化活性, 可抑制溶液中1,1-二苯基-2-苦基肼(DPPH)和2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐(ABTS)自由基的形成, 并呈剂量效应. 此外, ASPO能有效抑制5种肿瘤细胞的生长, 其中, A-375黑色素瘤细胞对ASPO具有良好的敏感性, 其IC50值为14.1 μg/mL. 对作用机制的研究发现, ASPO处理可诱导肿瘤细胞中 Sub-G1 凋亡峰的累积、 染色质固缩及凋亡小体的形成, 说明诱导细胞凋亡是 ASPO发挥抗肿瘤活性的主要机制. 进一步利用光谱滴定和黏度实验研究了ASPO与CT-DNA的相互作用, 发现ASPO以沟面结合方式与CT-DNA结合, 表明ASPO可能通过与DNA相互作用而触发肿瘤细胞凋亡通路.

关键词: 硒杂环衍生物, 抗氧化活性, 抗肿瘤活性, 凋亡, DNA相互作用

Abstract: The trace element selenium(Se) is an essential nutrient of fundamental importance to human and animal. Epidemiological, preclinical and clinical studies have supported the role of Se as potent cancer chemopreventive agents. Se-containing heterocyclic compounds have attracted more and more attention due to their anticancer potential and interesting chemical properties. In the present study, a selenadiazole pyrimidine heterocyclic derivative 5-amino-[1,2,5]selenadiazolo-[3,4-d]pyrimidin-7-ol(ASPO) was synthesized and characterized by ESI-MS, 1H NMR, elemental analysis, IR, UV-Vis absorption spectroscopy and fluorescence spectroscopy. Its antioxidant and anticancer activities were evaluated. The results show that ASPO can effectively scavenge the 2,2'-azinobis-3-ethylbenzothiazolin-6-sulfonic acid(ABTS) and 1,1-diphenyl-2-picryhydrazyl(DPPH) free radicals in a dose-dependent manner, demonstrating its strong antioxidant activity. The in vitro anticancer activities of ASPO were screened by MTT assay against various cancer cell lines and it was found that ASPO could effectively inhibit cancer cell growth, especially A-375 human melanoma cells. Further investigation on the action mode show that ASPO induces Sub-G1 peak accumulation, chromatin condensation and the formation of apoptotic bodies in a dose-dependent manner in A-375 cells, indicating that apoptosis is the main mechanism accounting for the anticancer action of ASPO. Moreover, it was showed that ASPO could bind to CT-DNA by minor groove. The results support that ASPO induces cancer cell apoptosis through its interaction with DNA.

Key words: Selenadiazole derivative, Antioxidant activity, Anticancer activity, Apoptosis, DNA Interaction

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