Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (7): 1741-1747.DOI: 10.6023/cjoc201701005 Previous Articles     Next Articles



郭亮a,b, 谢建伟a,b, 范文玺c, 陈伟c, 代斌a,b, 马芹c   

  1. a. 石河子大学化学化工学院 石河子 832003;
    b. 新疆兵团化工绿色过程重点实验室 石河子 832003;
    c. 新疆华世丹药物研究有限责任公司 乌鲁木齐 830011
  • 收稿日期:2017-01-04 修回日期:2017-03-07 发布日期:2017-03-17
  • 通讯作者: 代斌
  • 基金资助:


Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer

Guo Lianga,b, Xie Jianweia,b, Fan Wenxic, Chen Weic, Dai Bina,b, Ma Qinc   

  1. a. School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003;
    b. Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi 832003;
    c. Xinjiang Huashidan Pharmaceutical Research Co., Ltd., Urumqi 830011
  • Received:2017-01-04 Revised:2017-03-07 Published:2017-03-17
  • Contact: 10.6023/cjoc201701005
  • Supported by:

    Project supported by the Program for Outstanding Youth Science and Technology Innovation Talents Training in Xinjiang Uygur Autonomous Region (No.qn2015jc067).

In order to find novel antitumor candidate compounds with high efficiency and low toxicity, a series of 1-heterocyclic substituted bivalent β-carbolines with a spacer of four or five methylene units between the two 3-methylamino group were synthesized, and the chemical structures were characterized by 1H NMR, 13C NMR, and HRMS. The cytotoxic activities of all bivalent β-carbolines were evaluated in vitro against a panel of human tumor cell lines (22RV1, SK-OV-3, MCF-7, LLC, Eca-109, BGC-823, HT-29, HepG-2, A375, and 769-P) and compared with the positive control cisplatin and monovalent β-carbolines. The results demonstrated that compounds 5a~5h exhibited potent cytotoxic activities with IC50 values lower than 10 μmol·L-1. In particular, compounds 5d and 5h, both of which had a spacer of five methylene units, exhibited significant inhibitory activity against 769-P and 22RV1 with IC50 values of 0.8 μmol·L-1 and 0.6 μmol·L-1, respectively.

Key words: bivalent β-carboline, synthesis, antitumor activity, structure-activity relationship