Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (6): 2454-2466.DOI: 10.6023/cjoc202010029 Previous Articles     Next Articles



邵亮a, 杨帆a, 李唯嘉a, 俞飞a,b,*()   

  1. a 昆明理工大学医学院 昆明 650500
    b 北京大学天然药物与仿生药物国家重点实验室 北京 100191
  • 收稿日期:2020-10-21 修回日期:2020-12-15 发布日期:2021-02-22
  • 通讯作者: 俞飞
  • 作者简介:
    † 共同第一作者
  • 基金资助:
    云南省科技厅科技计划(2019FB125); 天然药物及仿生药物国家重点实验室开放基金(K202003)

Design, Synthesis and Anti-influenza A Virus Evaluation of Oleanolic Acid C3-Glycoconjugates

Liang Shaoa, Fan Yanga, Weijia Lia, Fei Yua,b()   

  1. a School of Medical, Kunming University of Science and Technology, Kunming 650500
    b State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191
  • Received:2020-10-21 Revised:2020-12-15 Published:2021-02-22
  • Contact: Fei Yu
  • About author:
    (These authors contributed equally to this work).
  • Supported by:
    Science and Technology Plan Project of Yunnan Provincial Department of Science and Technology(2019FB125); Open-Fund Program of the State Key Laboratory of Natural and Biomimetic Drugs(K202003)

Inhibitors targeting the entry stage of influenza viruses are a hot spot in the development of anti-influenza drugs. Our previous studies showed that oleanolic acid (OA) C28 glycoconjugates displayed strong anti-influenza virus activity. In this paper, a series of oleanolic acid C3 glycoconjugates 7a~14c were designed and synthesized via copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. The anti-influenza activities of all these compounds were evaluatedin vitro. Among them, oleanane-12-enyl-28-benzyloxycarbonyl-3-O-(4-methylene-1,2,3-triazole-1-(2,3,4,6-tetra-O-acetyl-β-D-galactoside)) (12a) showed the strongest activity with an IC50 of 12.45 µmol•L –1, and no obvious cytotoxic effect on MDCK cells was observed at 100 µmol•L –1. Hemagglutination inhibition and molecular docking experiments indicated that compound 12a might target viral envelope hemagglutinin (HA), thus inhibiting the attachment of viruses to host cells. This study improved the structure-activity relationships of oleanolic acid and its derivatives against influenza virus, and provided a basis for further research on anti-virus by these natural products.

Key words: oleanolic acid, glycoconjugates, influenza virus, CuAAC reaction, inhibitors