高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (3): 555-563.doi: 10.7503/cjcu20130543

• 有机化学 • 上一篇    下一篇

,4-三唑环的亚胺及酰亚胺类化合物的合成及生物活性

杨海葵1, 许万福2, 段安娜1, 游文玮1(), 赵培亮1()   

  1. 1. 南方医科大学药学院
    2. 基础医学院, 广州 510515
  • 收稿日期:2013-06-13 出版日期:2014-03-10 发布日期:2013-09-02
  • 作者简介:联系人简介: 赵培亮, 男, 博士, 副教授, 主要从事药物分子设计与合成研究. E-mail: plzhao@smu.edu.cn ; 游文玮, 男, 博士, 教授, 主要从事药物分子设计与合成研究. E-mail: youww@smu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号: 21372113)、 高等学校博士学科点专项科研基金(批准号: 20104433120011)和广州市珠江科技新星专项资助项目(批准号: 2012J2200051)资助

Syntheses and Biological Activities of Novel Imine and Imide Derivatives Bearing 1,2,4-Triazole Moiety

YANG Haikui1, XU Wanfu2, DUAN Anna1, YOU Wenwei1,*(), ZHAO Peiliang1,*()   

  1. 1. School of Pharmaceutical Sciences
    2. School of Basic Medical Sciences, Southern Medical Universtiy, Guangzhou 510515, China
  • Received:2013-06-13 Online:2014-03-10 Published:2013-09-02
  • Contact: YOU Wenwei,ZHAO Peiliang E-mail:youww@smu.edu.cn;plzhao@smu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.21372113), the Specialized Research Fund for the Doctoral Program of Higher Education(New Teachers), China(No.20104433120011), and the Project of Science and Technology New Star in Zhujiang Guangzhou City, China(No.2012J2200051)

摘要:

以取代苯甲酸为原料, 经酯化、 肼解、 成盐和环化反应得到关键中间体4-氨基-3-芳基-1,2,4-三唑-5-硫酮, 再分别与芳醛和邻苯二甲酸酐缩合得到亚胺及酰亚胺, 最后经硫醚化反应合成了24个新型的含有1,2,4-三唑结构单元的亚胺及酰亚胺类化合物, 其结构经质谱、 红外光谱、 核磁共振及元素分析确认. 初步生物活性测试结果表明, 在实验浓度下大部分化合物表现出一定的杀菌活性, 尤其是化合物9a, 9d和9e对水稻纹枯病菌的抑制活性与对照杀菌剂氟硅唑相当. 初步的细胞毒性实验结果表明, 化合物7c, 7f和9k对人肺癌细胞(A549)的抑制活性与对照药品5-氟尿嘧啶基本处于同一水平.

关键词: 1,2,4-三唑, 杀菌活性, 抗肿瘤活性

Abstract:

According to active groups combination principle, a series of novel imine and imide derivatives bearing 1,2,4-triazole moiety was designed and synthesized. The key intermediate 3-substituted phenyl-4-amino-1,2,4-triazole-5-thiones was synthesized by esterification, hydrazinolysis, salt and cyclization reactions, and then was condensed with aromatic aldehydes and isobenzofuran-1,3-dione to obtain imine and imide derivatives, which were subjected to the thioetherification with suitable halides(RX) to produce the corresponding 24 novel imine and imide derivatives bearing 1,2,4-triazole moiety. The structures of target compounds were fully characterized by 1H NMR, IR, mass spectroscopy and elemental analysis. The preliminary bioassay results showed that most of the compounds possessed certain fungicidal activities. At the concentration of 150 mg/L, the inhibition rates of compounds 9a, 9d and 9e against Rhizoctonia solani were very similar with the commercial fungicide Flusilazole. Meanwhile, the preliminary structure-activity relationships(SAR) were discussed in order to investigate the essential structures required for their bioactivities. In addition, their in vitro antitumor activities were evaluated against three cancer cell lines[human alveolar epithelial cells(A549), human breast cancer cells(MD-MBA-231) and human prostate cancer cells(PC-3M)] by the methyl thiazolyl tetrazolium(MTT) chromatometry method with Fluorouracil as a positive contrast drug. The bioassay data indicated that compounds 7c, 7f and 9k showed similar antiproliferation with Fluorouracil against A549 cell lines with IC50 values of 38.3, 44.6 and 36.7 μmol/L, respectively. Most interestingly, compound 9k also exhibited a broad spectrum of antitumor activity against MCF-7 and MKN45 with IC50 values of 147.5 and 60.7 μmol/L, respectively.

Key words: 1,2,4-Triazole, Fungicidal activity, Antitumor activity

中图分类号: