高等学校化学学报 ›› 2019, Vol. 40 ›› Issue (2): 254-261.doi: 10.7503/cjcu20180573

• 有机化学 • 上一篇    下一篇

N9位芳基取代嘌呤-8-酮类衍生物的合成及抗肿瘤活性

吕明君, 李雯, 杨新颖, 方浩()   

  1. 山东大学药学院药物化学教研室, 济南 250012
  • 收稿日期:2018-08-14 出版日期:2019-02-10 发布日期:2018-10-08
  • 作者简介:

    联系人简介: 方 浩, 男, 博士, 教授, 博士生导师, 主要从事抗肿瘤药物方面的研究. E-mail: haofangcn@sdu.edu.cn

  • 基金资助:
    国家自然科学基金(批准号: 21672127, 81874288)、 山东省重点研发计划(批准号: 2017CXGC1401)和山东大学自主创新基金(批准号: 2016JC018)资助

Synthesis and Antitumor Activity of N9 Position Aromatic Substituted Purine-8-one Derivatives

LÜ Mingjun, LI Wen, YANG Xinying, FANG Hao*()   

  1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
  • Received:2018-08-14 Online:2019-02-10 Published:2018-10-08
  • Contact: FANG Hao E-mail:haofangcn@sdu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(Nos.21672127, 81874288), the Key Research and Development Project of Shandong Province, China(No.2017CXGC1401) and the Fundamental Research Funds of Shandong University, China(No.2016JC018)

摘要:

合成了一系列N9位芳基取代嘌呤-8-酮类衍生物, 利用核磁共振氢谱(1H NMR)、 核磁共振碳谱(13C NMR)和高分辨质谱(HRMS)进行了结构确证. 采用四甲基偶氮唑盐(MTT)法测定了目标化合物的体外抗肿瘤细胞增殖活性. 结果表明, 嘌呤酮环的C2位及N9位的取代对活性有较大影响, C2位引入对位由含氮六元环取代的苯胺, N9位引入对三氟甲基苯均有利于提高抗肿瘤活性. 化合物12c对人白血病细胞(K562)、 人前列腺癌细胞(PC-3)、 人乳腺癌细胞(MDA-MB-231)及人结肠癌细胞(HCT116)的抑制效果明显优于阳性对照药R-Roscovitine.

关键词: 嘌呤衍生物, 合成, 抗肿瘤活性

Abstract:

A series of novel N9 position aromatic substituted purine-8-one derivatives was synthesized and the antitumor activities were evaluated in vitro. Chemical structures of target compounds were confirmed by means of nuclear magnetic resonance(NMR) and high resolution mass spectroscopy(HRMS). The antiproliferative acti-vities of target compounds were tested on a panel of tumor cell lines using thiazolyl blue tetrazolium bromide(MTT) assay. The results revealed that the substitutions on C2 and N9 position had great impacts on antitumor activities. Moreover, introducing aniline attached six-member ring on C2 position or p-CF3 on N9 position could improve the antitumor activities. Importantly, the most potent compound 12c exhibited better inhibitory activities than R-Roscovitine against four tumor cell lines, including human leukemia cell lines(K562), human prostatic carcinoma cell lines(PC-3), human breast cancer cell lines(MDA-MB-231) and human colon cancer cell lines(HCT116).

Key words: Purine derivative, Synthesis, Antitumor activity

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