Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (5): 1453-1462.DOI: 10.6023/cjoc202111008 Previous Articles     Next Articles



蔡铭a, 邵亮a, 杨帆a, 张继虹a, 俞飞a,b,*()   

  1. a 昆明理工大学医学院 昆明 650500
    b 北京大学药学院 天然药物及仿生药物国家重点实验室 北京 100191
  • 收稿日期:2021-11-03 修回日期:2021-12-31 发布日期:2022-01-27
  • 通讯作者: 俞飞
  • 基金资助:
    国家自然科学基金(22167018); 天然药物及仿生药物国家重点实验室开放基金(K202003); 云南省科技厅科技计划(2019FB125); 云南省科技厅科技计划(2018FB145)

Design, Synthesis of Pentacyclic Triterpenoid Glucose Conjugate and in vitro Activity against Influenza Virus

Ming Caia, Liang Shaoa, Fan Yanga, Jihong Zhanga, Fei Yua,b()   

  1. a Medical Faculty, Kunming University of Science and Technology, Kunming 650500
    b State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191
  • Received:2021-11-03 Revised:2021-12-31 Published:2022-01-27
  • Contact: Fei Yu
  • Supported by:
    National Natural Science Foundation of China(22167018); Foundation of State Key Laboratory of Natural and Biomimetic Drugs(K202003); Yunnan Fundamental Research Projects(2019FB125); Yunnan Fundamental Research Projects(2018FB145)

Previous studies have revealed that oleanolic acid (OA) C28-glucose conjugate displayed potent anti-influenza viral activity in vitro. However, the effect of pentacyclic triterpene scaffold coupled with glucose on anti-influenza virus activity has not been clarified. Herein, as a continuous further study, a series of pentacyclic triterpene-glucose conjugates were prepared via CuAAC reaction, and the anti-influenza activity of these compounds was evaluated in vitro. Among them, compound 4d, an betulinic acid (BA)-glucose conjugate, showed potent anti-influenza virus activity (IC50 value of 9.09 μmol/L), and no obvious cytotoxic effect on MDCK (Madin-Darbey Canine Kidney) cells was observed (CC50>100 μmol/L). Structure-activity relationship studies showed that both triterpene scaffolds and glucose moiety have important effects on the anti-viral activity. Overall, this finding further extends the utility of triterpene derivatives in anti-influenza virus drug design.

Key words: pentacyclic triterpene, influenza virus, entry inhibitors, structure-activity relationship