Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (4): 1037-1043.DOI: 10.6023/cjoc201808016 Previous Articles     Next Articles

Articles

新型含1,3,4-噁二唑片段硫色满酮衍生物的设计、合成及其抗真菌活性研究

孙晓阳a, 冯佳佳a, 李生彬a, 冯思冉a, 刘振明c, 宋亚丽a, 乔晓强a,b   

  1. a 河北大学药学院 河北省药物质量分析控制重点实验室 保定 071000;
    b 河北大学 药物化学与分子诊断教育部重点实验室 保定 071000;
    c 北京大学药学院 天然药物及仿生药物国家重点实验室药物设计中心 北京 100191
  • 收稿日期:2018-08-16 修回日期:2018-11-13 出版日期:2019-04-25 发布日期:2018-12-28
  • 通讯作者: 宋亚丽, 乔晓强 E-mail:yalisong@hbu.edu.cn;xiaoqiao@hbu.edu.cn
  • 基金资助:

    河北省自然科学基金(No.B2018201269)、国家自然科学基金(No.21675039)、中国博士后科学基金(No.2016M591401)、河北省青年拔尖人才、河北大学杰出青年科学基金(No.2015JQ06)资助项目.

Design, Synthesis, and Antifungal Activity of Novel Thiochromanone Derivatives Containing 1,3,4-Oxadiazole Skeleton

Sun Xiaoyanga, Feng Jiajiaa, Li Shengbina, Feng Sirana, Liu Zhenmingc, Song Yalia, Qiao Xiaoqianga,b   

  1. a Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmacy, Heibei University, BaoDing 071000;
    b Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Heibei University, BaoDing 0710004;
    c Drug Design Center, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191
  • Received:2018-08-16 Revised:2018-11-13 Online:2019-04-25 Published:2018-12-28
  • Contact: 10.6023/cjoc201808016 E-mail:yalisong@hbu.edu.cn;xiaoqiao@hbu.edu.cn
  • Supported by:

    Project supported by the Natural Science Foundation of Hebei Province (No.B2018201269),the National Natural Science Foundation of China (No.21675039),the China Postdoctoral Science Foundation (No.2016M591401),the Young Talent of Hebei Province,and the Hebei University Science Fund for Distinguished Young Scholars (No.2015JQ06).

Following the principle of union of active group, the thiochromanone was combined with 1,3,4-oxadiazole, and 12 compounds were designed and synthesized. The target compounds were confirmed by 1H NMR and HRMS. The preliminary antifungal activity assay showed that most of the target compounds exhibited significant inhibition activity against four animal pathogenic fungi and four plant pathogenic fungi. Among them, the minimum inhibitory concentration (MIC) value of compound 4f against Canidia albicans reached 4 μg·mL-1, and the MIC value of 4d against Aspergillusnigervan tiegh reached 8 μg·mL-1, which were higher than the positive controls. And the molecular docking studies have found that 4f has strong binding ability to CYP51 of Canidia albicans, which may be a potential CYP51 inhibitor.

Key words: thiochromanone, 1,3,4-oxadiazole, antifungal, molecular docking