Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (8): 3321-3329.DOI: 10.6023/cjoc202102031 Previous Articles     Next Articles



陆棋a, 叶飞霞a, 孙晓彤a, 翁建全a,*(), 余茜b,*(), 胡德玄c   

  1. a 浙江工业大学化学工程学院 杭州 310014
    b 广东药科大学临床药学院 广州 510006
    c 中山大学药学院 广州 510006
  • 收稿日期:2021-02-19 修回日期:2021-04-16 发布日期:2021-05-14
  • 通讯作者: 翁建全, 余茜
  • 基金资助:

Design and Synthesis of Novel Nature-Inspired Stilbene Analogues as Potential Topoisomerase 1 Inhibitors

Qi Lua, Feixia Yea, Xiaotong Suna, Jianquan Wenga(), Qian Yub(), Dexuan Huc   

  1. a College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014
    b School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006
    c School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006
  • Received:2021-02-19 Revised:2021-04-16 Published:2021-05-14
  • Contact: Jianquan Weng, Qian Yu
  • Supported by:
    Natural Science Foundation of Zhejiang Province(LY17C140003)

In order to find novel antitumor drug leads, twenty-three nature-inspired stilbene analogues containing thiazole moiety were designed and synthesized, and their structures were confirmed by NMR and ESI-HRMS. These compounds were screened for their topoisomerase I (Top1) inhibitory activity using Top1-mediated relaxation assay, and (E)-5-bromo-2- (2-chlorostyryl)-4-(4-fluorophenyl)thiazole (6k) possessed promising Top1 inhibitory activity. Molecular docking was also established to study the structure-activity relationship and a good correlation was observed between Top1 inhibitory activity and molecular docking study. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against human breast cancer (MCF-7) and human colon cancer (HCT116) cell lines indicated that (E)-5-bromo-4-(4-fluorophenyl)- 2-(4-(trifluoromethyl)styryl)thiazole (6e), (E)-5-bromo-2-(2-chlorostyryl)-4-(4-fluorophenyl)thiazole (6k), and (E)-5-bromo- 2-(4-chlorostyryl)-4-(4-fluorophenyl)thiazole (6l) showed high cytotoxicity at low micromolar concentrations.

Key words: natural stilbene, thiazole, topoisomerase 1 inhibitor, synthesis, cytotoxicity