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2023 , Vol. 43 >Issue 7: 2543 - 2552

DOI: https://doi.org/10.6023/cjoc202210040

研究论文

2,5-二氨基噻吩-3,4-二羧酸二乙酯衍生物的合成及抗肿瘤活性研究

  • 张维舒 ,
  • 聂礼飞 ,
  • Khurshed Bozorov ,
  • 阿吉艾克拜尔?艾萨 ,
  • 赵江瑜
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  • a中国科学院新疆理化技术研究所 新疆特有药用资源利用重点实验室 乌鲁木齐 830011
    b中国科学院大学 北京 100049
    c撒马尔罕国立大学化学学院 撒马尔罕 乌兹别克斯坦 140104

收稿日期: 2022-10-30

  修回日期: 2023-01-08

  网络出版日期: 2023-02-07

基金资助

国家重点研发计划(2020YFE0205600)

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Synthesis of Diethyl 2,5-Diaminothiophene-3,4-dicarboxylate Derivatives and Antitumor Activity Study

  • Weishu Zhang ,
  • Lifei Nie ,
  • Khurshed Bozorov ,
  • Haji Akber Aisa ,
  • Jiangyu Zhao
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  • aState Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011
    bUniversity of Chinese Academy of Sciences, Beijing 100049
    cFaculty of Chemistry, Samarkand State University, Samarkand, Uzbekistan 140104
*E-mail:

Received date: 2022-10-30

  Revised date: 2023-01-08

  Online published: 2023-02-07

Supported by

National Key R&D Program of China(2020YFE0205600)

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摘要

以含硫杂环噻吩为母核, 设计并合成了30个2,5-二氨基噻吩-3,4-二羧酸二乙酯衍生物, 经1H NMR、13C NMR和HRMS进行了结构确证. 用噻唑蓝(MTT)法测定该系列化合物对HeLa(人宫颈癌)、HT-29(人结肠癌)、A549(人非小细胞肺癌)、HepG2(人肝癌)四种肿瘤细胞的体外抗增殖活性. 结果表明, 部分化合物表现出良好的抗增殖活性, 其中2-(4-(三氟甲氧基)苯甲酰胺基-5-(5-硝基噻吩-2-基)亚甲基氨基噻吩-3,4-二羧酸二乙酯(C25)对HT-29、A549两种肿瘤细胞均表现出明显的抗增殖活性, IC50值分别为(0.35±0.07)和(0.66±0.09) μmol/L; 2-(3-(三氟甲基)苯甲酰胺基)-5-(5-硝基噻吩-2-基)亚甲基氨基噻吩-3,4-二羧酸二乙酯(C29)对HT-29、HepG2两种肿瘤细胞也表现出明显的抗增殖活性, IC50值分别为(0.47±0.03)和(0.41±0.04) μmol/L, 其抑制活性均优于阳性对照药阿霉素(DOX)[对HT-29、A549、HepG2的IC50值分别为(1.15±0.03)、(0.86±0.07)、(0.86±0.02) μmol/L].

关键词： 2,5-二氨基噻吩-3,4-二羧酸二乙酯; 抗肿瘤活性

本文引用格式

张维舒 , 聂礼飞 , Khurshed Bozorov , 阿吉艾克拜尔?艾萨 , 赵江瑜 . 2,5-二氨基噻吩-3,4-二羧酸二乙酯衍生物的合成及抗肿瘤活性研究[J]. 有机化学, 2023 , 43(7) : 2543 -2552 . DOI: 10.6023/cjoc202210040

Abstract

Based on the sulfur heterocyclic compound thiophene, thirty diethyl 2,5-diaminothiophene-3,4-dicarboxylate derivatives were designed and synthesized. The structures of all compounds were confirmed by 1H NMR, 13C NMR and HRMS, and antiproliferative activities of the target compounds against four human cancer cell lines (HeLa, HT-29, A549 and HepG2) were evaluated by methyl thiazolyl tetrazolium (MTT) in vitro. The results showed that some compounds exhibited good anticancer activity. Especially, diethyl 2-(4-(trifluoromethoxy)benzamido-5-(5-nitrothiophen-2-yl)methylene-aminothiophene- 3,4-dicarboxylate (C25) possessed the best activity, whose IC50 values were (0.35±0.07) and (0.66±0.09) μmol/L against HT-29 and A549, respectively; diethyl 2-(3-(trifluoromethyl)benzamido-5-(5nitrothiophen-2-yl)methyleneaminothiophene- 3,4-dicarboxylate (C29) also possessed the best activity, whose IC50 values were (0.47±0.03) and (0.41±0.04) μmol/L against HT-29 and HepG2, respectively, better than positive control drug doxorubicin (DOX) (IC50 values were (1.15±0.03), (0.86±0.07) and (0.86±0.02) μmol/L against HT-29, A549, and HepG2, respectively).

Key words： diethyl 2,5-diaminothiophene-3,4-dicarboxylate; anticancer activity

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