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一氧化氮供体型烷氧基联苯化合物的合成及抗肿瘤活性

谷小珂, 唐孝波, 黄张建, 彭晖, 张奕华

谷小珂, 唐孝波, 黄张建, 彭晖, 张奕华. 一氧化氮供体型烷氧基联苯化合物的合成及抗肿瘤活性[J]. 中国药科大学学报, 2014, 45(6): 657-661. DOI: 10.11665/j.issn.1000-5048.20140606
引用本文: 谷小珂, 唐孝波, 黄张建, 彭晖, 张奕华. 一氧化氮供体型烷氧基联苯化合物的合成及抗肿瘤活性[J]. 中国药科大学学报, 2014, 45(6): 657-661. DOI: 10.11665/j.issn.1000-5048.20140606
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GU Xiaoke, TANG Xiaobo, HUANG Zhangjian, PENG Hui, ZHANG Yihua. Synthesis and antitumor activity of NO-releasing alkoxylbiphenyl derivatives[J]. Journal of China Pharmaceutical University, 2014, 45(6): 657-661. DOI: 10.11665/j.issn.1000-5048.20140606
Citation: GU Xiaoke, TANG Xiaobo, HUANG Zhangjian, PENG Hui, ZHANG Yihua. Synthesis and antitumor activity of NO-releasing alkoxylbiphenyl derivatives[J]. Journal of China Pharmaceutical University, 2014, 45(6): 657-661. DOI: 10.11665/j.issn.1000-5048.20140606
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一氧化氮供体型烷氧基联苯化合物的合成及抗肿瘤活性

  • 1.

    徐州医学院江苏省新药研究与临床药学重点实验室

  • 2.

    中国药科大学新药研究中心

  • 3.

    军事医学科学院卫生学环境医学研究所

基金项目: 国家自然科学基金资助项目(No.81402789)

Synthesis and antitumor activity of NO-releasing alkoxylbiphenyl derivatives

摘要

    摘要
  • 摘要: 基于药物设计的拼合原理，将一氧化氮(NO)供体片段联接到烷氧基联苯结构中，设计、合成了一系列NO供体型烷氧基联苯化合物。采用MTT法评价了目标化合物对人肝癌细胞系HepG-2、Bel-7402、SMMC-7721、QGY-7701及Bel-7404的增殖抑制作用。结果表明，目标化合物( 4a ~ 4g )对5种肝癌细胞均呈现出较好的抑制作用，其中对HepG-2的活性最强(IC50=1.15~4.34 μmol/L)。值得注意的是，除化合物 4f 外，其他化合物对正常肝细胞LO2的抑制作用较小(IC50=5.00~8.53 μmol/L)，提示NO供体型烷氧基联苯化合物对肝肿瘤细胞具有一定的选择性。此外，化合物 4b 对敏感及耐药的K562细胞均具有显著的增殖抑制作用，其IC50分别为1.32和1.28 μmol/L。加入NO清除剂后，化合物 4b 的抑制活性显著降低，提示该化合物释放的NO对其抗肿瘤活性具有重要贡献。
    Abstract: A series of NO-releasing alkoxylbiphenyl derivatives( 4a - 4g )were designed and synthesized by coupling the carboxyl group of alkoxylbiphenyl with NO donor. Their antitumor activities were evaluated by MTT assay in HepG-2, Bel-7402, SMMC-7721, QGY-7701 and Bel-7404 cell lines. The results indicated that the target compounds exhibited significant inhibitory effects on the proliferation of tumor cells, especially on HepG-2 cells(IC50=1. 15-4. 34 μmol/L). Notably, the inhibitory effect of the target compounds on non-tumor liver LO2 cells was relatively weak(IC50=5. 00-8. 53 μmol/L)except compound 4f , suggesting that these compounds have selective inhibitory effects on tumor cells in vitro. Additionally, compound 4b could significantly inhibit the parental sensitive K562 and drug-resistant K562/A02 cell proliferation, and the IC50s were 1. 28 and 1. 32 μmol/L, respectively. Importantly, treatment with various concentrations of an NO scavanger significantly reduced the antitumor activity of compound 4b , suggesting that NO produced by compound 4b may play a significant role in inhi-biting the proliferation of K562 and K562/A02 cells.
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    • 参考文献(13)
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  • 刊出日期:  2014-12-24

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