论著·基础研究

以6,11-二氢-5H-苯并[a]咔唑优势结构为基础的抑制宫颈癌细胞增殖先导化合物的发现

  • 董亚 ,
  • 杨若林 ,
  • 沈征武 ,
  • 刘坚华
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  • 上海交通大学基础医学院化学教研室,上海 200025
董亚(1993—),女,硕士生;电子信箱:DY1993@sjtu.edu.cn。

网络出版日期: 2018-07-03

基金资助

国家自然科学青年基金(81402775);国家教育部博士点基金资助项目(20130073120113)

Discovery of lead compounds to inhibit proliferation of cervical cancer cells based on privileged structure of 6,11-dihydro-5H-benzo[a]carbazole

  • DONG Ya ,
  • YANG Ruo-lin ,
  • SHEN Zheng-wu ,
  • LIU Jian-hua
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  • Department of Chemistry, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China

Online published: 2018-07-03

Supported by

National Natural Science Youth Fund, 81402775; PhD. Programs Foundation of Ministry of Education of China, 20130073120113

摘要

目的·发现以6,11-二氢-5H-苯并[a]咔唑环为母核可抑制宫颈癌细胞增殖的先导化合物。方法·用Fisher吲哚合成法制备了一系列6,11-二氢-5H-苯并[a]咔唑类化合物及其类似物,并在体外用CCK8法测试了这些化合物对HeLa细胞增殖的抑制作用。结果· 2-甲氧基-6,11-二氢-5H-苯并[a]咔唑和8-氯-2-甲氧基-6,11-二氢-5H-苯并[a]咔唑具有良好的抑制HeLa细胞增殖的活性,其半数抑制浓度(IC50)值分别为9.61 μmol/L和16.52 μmol/L。结论·发现2个目标先导化合物。在6,11-二氢-5H-苯并[a]咔唑类衍生物中,母环2位C上为甲氧基取代的衍生物具有较好的抗宫颈癌细胞增殖活性。

本文引用格式

董亚 , 杨若林 , 沈征武 , 刘坚华 . 以6,11-二氢-5H-苯并[a]咔唑优势结构为基础的抑制宫颈癌细胞增殖先导化合物的发现[J]. 上海交通大学学报(医学版), 2018 , 38(6) : 605 . DOI: 10.3969/j.issn.1674-8115.2018.06.004

Abstract

Objective · To discover lead compounds with 6,11-dihydro-5H-benzo[a]carbazole as core scaffold that can inhibit the proliferation of cervical cancer cells. Methods · A series of 6,11-dihydro-5H-benzo[a]carbazole derivatives and analogs were synthesized using Fischer indole synthesis method, and their anticancer activity against HeLa cells was tested in vitroCCK8 test. Results · 2-Methoxy-6,11-dihydro-5H-benzo[a]carbazole and 8-chloro-2methoxy- 6,11-dihydro-5H-benzo[a]carbazole could significantly inhibit the proliferation of HeLa cells with the half maximal inhibitory concentration (IC50)values of 9.61 μmol/L and 16.52 μmol/L, respectively. Conclusion · Two objective lead compounds were found. Among 6,11-dihydro-5H-benzo[a]carbazole derivatives, compounds with methoxy group at the C-2 position of the core scaffold show better activity against proliferation of cervical cancer cells.
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