有机化学 ›› 2018, Vol. 38 ›› Issue (4): 949-954.DOI: 10.6023/cjoc201711005 上一篇    下一篇

研究简报

新型3-芳基-5-呋喃基-4,5-二氢异噁唑啉衍生物的合成及其细胞毒活性

黎勇坤a, 刘蓓a, 张丽君a, 朱加洪a, 万春平b, 毛泽伟a   

  1. a 云南中医学院中药学院 昆明 650500;
    b 云南中医学院第一附属医院中心实验室 昆明 650021
  • 收稿日期:2017-11-02 修回日期:2017-12-04 发布日期:2017-12-15
  • 通讯作者: 万春平, 毛泽伟 E-mail:wanchunping1012@163.com;maozw@ynutcm.edu.cn
  • 基金资助:

    国家自然科学基金(No.81460624)和云南省科学技术厅-云南中医学院应用基础研究联合专项(No.2017FF117(-023))资助项目.

Synthesis and Cytotoxic Activity of New 3-Aryl-5-furanyl-4, 5-dihydroisoxazoline Derivatives

Li Yongkuna, Liu Beia, Zhang Lijuna, Zhu Jiahonga, Wan Chunpingb, Mao Zeweia   

  1. a College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Kunming 650500;
    b Central Laboratory, The No.1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming 650021
  • Received:2017-11-02 Revised:2017-12-04 Published:2017-12-15
  • Contact: 10.6023/cjoc201711005 E-mail:wanchunping1012@163.com;maozw@ynutcm.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81460624) and the Yunnan Provincial Science and Technology Department-Applied Basic Research Joint Special Funds of Yunnan University of Traditional Chinese Medicine (No. 2017FF117 (-023))

异噁唑啉是一类具有广泛生物活性的杂环化合物.采用活性亚结构拼接的思路,在前期研究基础上,设计合成了10个未见文献报道的新型3-[4-(1-哌嗪基)]苯基-5-(2-呋喃基)-4,5-二氢异噁唑啉衍生物3~12,其结构经IR、1H NMR、13C NMR和HRMS确证.采用噻唑蓝(MTT)法测试了目标化合物的体外细胞毒活性(Hela、A549和SGC7901).结果表明,该类化合物普遍具有良好的细胞毒活性,特别是化合物4、611对肿瘤细胞株的体外抑制活性与阳性对照药5-氟尿嘧啶相当.进一步的流式细胞分析结果表明,化合物411均能有效诱导肿瘤细胞株A549的死亡.

关键词: 二氢异噁唑啉, 合成, 细胞毒活性, 流式细胞分析

Dihydroisoxazoline is a heterocyclic compound with a variety of biological properties. In this study, ten new 3-(4-piperazinyl)phenyl-5-(2-furyl)-4,5-dihydroisoxazoline derivatives (3~12) have been prepared by the general principle of molecular hybridization based on former work. The structures were characterized by IR, 1H NMR, 13C NMR and HRMS. In vitro cytotoxic activity against a panel of human tumor cell lines (Hela, A549 and SGC7901) was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The result indicated that dihydroisoxazoline derivatives showed potential cytotoxic activity, and the substituents of the NH group of piperazine ring had an obvious influence on cytotoxic activities. Especially, compound 4, 6 and 11 were found to be better inhibition against human tumor cell lines, which were found to be similar cytotoxic activity to positive control 5-fluorouracil. Further FACs analysis showed that compounds 4 and 11 significantly induced death in A549 cell.

Key words: dihydroisoxazoline, synthesis, cytotoxic activity, FACs analysis