有机化学 ›› 2017, Vol. 37 ›› Issue (7): 1741-1747.DOI: 10.6023/cjoc201701005 上一篇    下一篇

研究论文

双-(1-杂环-β-咔啉)-3-烷氨基衍生物的合成与抗肿瘤活性

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 出版日期:2017-07-25 发布日期:2017-03-17
  • 通讯作者: 代斌 E-mail:db_tea@shzu.edu.cn
  • 基金资助:

    新疆维吾尔自治区青年科技创新人才培养工程(No.qn2015jc067)资助项目

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 Online:2017-07-25 Published:2017-03-17
  • Contact: 10.6023/cjoc201701005 E-mail:db_tea@shzu.edu.cn
  • Supported by:

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

为寻找高效、低毒的抗肿瘤候选化合物,以1-杂环取代-β-咔啉-3-羧酸乙酯为原料,合成了一系列的双-(1-杂环-β-咔啉)-3-烷氨基衍生物.所有目标化合物经1H NMR、13C NMR和HRMS进行结构确证.以顺铂为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(22RV1,SK-OV-3,MCF-7,BGC-823,A375和769-P等10株细胞)活性.结果显示化合物5a~5h与阳性对照药和单取代β-咔啉衍生物相比具有很好的抗肿瘤活性,其IC50值均小于10μmol·L-1,特别是化合物5d对769-P的抑制活性达到0.8 μmol·L-1,化合物5h对22RV1的抑制活性达到0.6 μmol·L-1.

关键词: β-咔啉, 合成, 抗肿瘤活性, 构效关系

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