有机化学 ›› 2019, Vol. 39 ›› Issue (9): 2507-2514.DOI: 10.6023/cjoc201902033 上一篇    下一篇

研究论文

4-取代-1-(2-甲基-6-(吡啶-3-基)-烟酰)氨基脲类衍生物合成与生物活性研究

胡鸿雨a, 吴俊b, 袁建锋a, 王珍妮a, 李晨帆a, 严晓阳a, 方美娟b, 赵胜贤a,c   

  1. a 浙江师范大学行知学院 金华 321004;
    b 厦门大学药学院 厦门 361102;
    c 宁波大学科学技术学院 慈溪 315302
  • 收稿日期:2019-02-27 修回日期:2019-04-10 出版日期:2019-09-25 发布日期:2019-05-10
  • 通讯作者: 方美娟, 赵胜贤 E-mail:fangmj@xmu.edu.cn;2086488660@qq.com
  • 基金资助:

    浙江省教育厅一般课题基金(No.Y201941989)资助项目.

Synthesis and Biological Activity Research of 4-Substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) Semicarbazides

Hu Hongyua, Wu Junb, Yuan Jianfenga, Wang Zhennia, Li Chenfana, Yan Xiaoyana, Fang Meijuanb, Zhao Shengxiana,c   

  1. a Xingzhi College, Zhejiang Normal University, Jinhua 321004;
    b School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102;
    c College of Science and Technology, Ningbo University, Cixi 315302
  • Received:2019-02-27 Revised:2019-04-10 Online:2019-09-25 Published:2019-05-10
  • Contact: 10.6023/cjoc201902033 E-mail:fangmj@xmu.edu.cn;2086488660@qq.com
  • Supported by:

    Project supported by the General Research Projects of Zhejiang Provincial Department of Education (No. Y201941989).

经分子杂交技术[A1]合成了一系列4-取代-1-(2-甲基-6-(吡啶-3-基)-烟酰)氨基脲类衍生物.采用噻唑蓝(MTT)比色法研究了目标化合物对人肝癌细胞(QGY-7703)、人肺癌细胞(NCl-H460)和乳腺癌细胞(MCF-7)的体外抗肿瘤活性.1-(2-甲基-6-(吡啶-3-基)烟酰基)-4-(2,4,6-三氯苯基)氨基脲(4n)显示了最优的活性,其半数抑制浓度(IC50)为8.89~11.45 μmol/L.细胞体内的生物研究显示,4n药物[A2]处理能明显增加细胞体内PARP切割水平以及诱导QGY-7703肿瘤细胞的凋亡.

关键词: 氨基脲, 联吡啶, 分子杂交, 生物活性

A series of 4-substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) semicarbazides were synthesized[A3] via molecular hybridization strategy. The synthesized compounds were screened for their anticancer potential against different cancer cells viz human hepatocelular carcinoma (QGY-7703), non-small cell lung (NCl-H460) and human breast (MCF-7) cancer cell lines by methyl thiazolyl tetrazolium (MTT) assay. 1-(2-Methyl-6-(pyridin-3-yl)nicotinoyl)-4-(2,4,6-trichlorophenyl)semicarbazide (4n) showed significant anticancer activity in these cancer cell lines with a range of IC50 values from 8.89 μmol/L to 11.45 μmol/L. Further biology studies showed that 4n treatment obviously increased the level of cleaved PARP and induced the apoptosis in QGY-7703 cells.

Key words: semicarbazides, bipyridine, molecular hybridization, biological activity