有机化学 ›› 2019, Vol. 39 ›› Issue (9): 2581-2588.DOI: 10.6023/cjoc201903004 上一篇    下一篇

研究论文

含芳硫醚结构的新型酰胺衍生物的设计、合成和生物活性

华学文a, 刘南南a, 范志金b, 宗广宁b, 马翼b, 雷康c, 殷昊a, 王桂清a   

  1. a 聊城大学农学院 聊城 252000;
    b 南开大学元素有机化学国家重点实验室 天津 300071;
    c 聊城大学药学院 聊城 252000
  • 收稿日期:2019-03-03 修回日期:2019-03-31 出版日期:2019-09-25 发布日期:2019-04-19
  • 通讯作者: 华学文 E-mail:huaxuewen906@163.com
  • 基金资助:

    山东省自然科学基金(No.ZR2017BC053)、聊城大学博士科研启动基金(No.318051625)、聊城大学大学生创新创业训练(No.CXCY2018181)资助项目.

Design, Synthesis and Biological Activity Screening of Novel Amide Derivatives Containing Aromatic Thioether Group

Hua Xuewena, Liu Nannana, Fan Zhijinb, Zong Guangningb, Ma Yib, Lei Kangc, Yin Haoa, Wang Guiqinga   

  1. a College of Agriculture, Liaocheng University, Liaocheng 252000;
    b State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071;
    c College of Pharmacy, Liaocheng University, Liaocheng 252000
  • Received:2019-03-03 Revised:2019-03-31 Online:2019-09-25 Published:2019-04-19
  • Contact: 10.6023/cjoc201903004 E-mail:huaxuewen906@163.com
  • Supported by:

    Project supported by the Natural Science Foundation of Shandong Province (No. ZR2017BC053), the Doctoral Research Startup Foundation of Liaocheng University (No. 318051625), and the Innovation and Entrepreneurship Training Program for College Students of Liaocheng University (No. CXCY2018181).

在前期工作中,含芳硫醚(砜)结构的系列酰胺衍生物在200 μg/mL浓度下显示出了优异的杀线虫活性.为了细致研究氟吡菌酰胺中酰胺桥结构修饰对生物活性的影响,通过采取酰胺键翻转、引入N-磺酰基取代的酰胺键,设计、合成了两系列结构新颖的含芳硫醚的酰胺化合物.生物活性测定显示,酰胺桥结构修饰对目标化合物的杀线虫活性和杀菌活性影响较大.其中,相对于化合物I,化合物Ⅱ中酰胺键上N-磺酰基的引入有利于改善杀线虫活性.分子对接发现,酰胺桥中羰基或者磺酰基与芳香环直接相连对杀线虫活性是有利的.

关键词: 合成, 硫醚, 酰胺, 杀线虫活性, 分子对接

A series of amide derivatives containing aromatic sulfide and sulfone groups synthesized in our previous work displayed excellent nematocidal activity at 200 μg/mL. In order to explore the effect of structural modification of the amide bridge on biological activity in a more delicate way, two series of novel target compounds were designed and synthesized by adopting amide group flipping and introducing N-sulfonyl substituted amide bonds. The bioassays indicated that the structural modification of the amide bridge had important effects on their nematocidal and fungicidal activities, which the introduction of the N-sulfonyl substituent on the amide group was favorable to improving the nematocidal activity in comparison with compounds I. The molecular docking revealed that directly attaching the carbonyl or sulfonyl groups in the amide bridge to the aromatic rings was advantageous to the nematocidal activity.

Key words: synthesis, thioether, amide, nematocidal activity, molecular docking