研究论文

新型3-取代苯甲酰基-4-取代噻吩基吡咯类化合物的合成及抗肿瘤活性研究

  • 陈简 ,
  • 张袁魁 ,
  • 詹晓平 ,
  • 刘增路 ,
  • 毛振民
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  • 上海交通大学药学院 上海 200240

收稿日期: 2015-10-14

  修回日期: 2015-11-06

  网络出版日期: 2015-11-20

基金资助

国家科技重大新药创制专项(No. 2010ZX09401404-004)资助项目.

Synthesis and Anti-tumor Activity of Novel 3-Substituted-benzoyl-4-substituted-thienyl-pyrroles

  • Chen Jian ,
  • Zhang Yuankui ,
  • Zhan Xiaoping ,
  • Liu Zenglu ,
  • Mao Zhenmin
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  • School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240

Received date: 2015-10-14

  Revised date: 2015-11-06

  Online published: 2015-11-20

Supported by

Project supported by the National Science and Technology Major Special Drug Discovery (No. 2010ZX09401404-004).

摘要

以取代苯乙酮和取代噻吩-2-甲醛为原料, 经过Aldol缩合和Van Leusen吡咯合成法合成了29个未见文献报道的3-取代苯甲酰基-4-取代噻吩基吡咯类化合物2a~5c. 以噻唑蓝(MTT)法测定目标化合物对人结肠癌细胞 (HCT-116)、人胃腺癌细胞(SGC-7901)、人宫颈癌细胞(Hela)和H人脐静脉血管内皮细胞(UVEC)的细胞增殖抑制活性, 结果显示化合物2c, 2i, 3i, 3j, 4a~4f5c对HCT-116细胞有较强(IC50≤20 μmol·L-1)或中等(20 μmol·L-150≤50 μmol·L-1)增殖抑制作用; 化合物2j对Hela细胞有较强增值抑制作用, 其IC50值为4.3 μmol·L-1, 化合物2i, 3j对Hela细胞有中等增殖抑制作用; 化合物3j对SGC-7901细胞有较强增殖抑制作用, 化合物2i对SGC-7901细胞有中等增殖抑制作用. 几乎所有化合物对HUVEC细胞无显著增殖抑制作用, 具有高选择性.

本文引用格式

陈简 , 张袁魁 , 詹晓平 , 刘增路 , 毛振民 . 新型3-取代苯甲酰基-4-取代噻吩基吡咯类化合物的合成及抗肿瘤活性研究[J]. 有机化学, 2016 , 36(3) : 572 -579 . DOI: 10.6023/cjoc201510016

Abstract

29 novel 3-substituted-benzoyl-4-substituted-thienyl-pyrrole compounds 2a~5c were synthesized via aldol condensation and Van Leusen pyrrole reaction using substituted acetophenone and substituted 2-thenaldehyde as raw materials, and the cell proliferation inhibition efficacy of 2a~5c against human colon cancer (HCT-116), human gastric adenocarcinoma (SGC-7901), human cervical carcinoma (Hela) and human umbilical vein endothelial (HUVEC) cell lines were estimated. Then MTT assay was used to evaluate the anti-proliferative activity. The result indicated that some target compounds exhibited strong (IC50≤20 μmol·L-1) or moderate (20 μmol·L-150≤50 μmol·L-1) proliferation inhibition efficacy against tumor cells, meanwhile didn't have significate inhibition effect on HUVEC. Compounds 2c, 2i, 3i, 3j, 4a~4f and 5c showed strong or moderate inhibition efficacy against HCT-116. The IC50 value of 2j was 4.3 μmol·L-1 against Hela, and compounds 2i and 3j exhibited moderate inhibition efficacy against Hela. The IC50 value of 3j was 10.5 μmol·L-1 against SGC-7901, and compounds 2i indicated moderate inhibition efficacy against SGC-7901. Compounds 2i and 3j showed broad anti-proliferative activity against all selected tumor cells.

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