有机化学 ›› 2019, Vol. 39 ›› Issue (4): 1064-1069.DOI: 10.6023/cjoc201809003 上一篇    下一篇

研究论文

1,3,4-噻二唑三氮烯化合物的合成和生物活性研究

张明千, 刘斌凯, 雷强, 颜景东, 赵中玉, 龙跃   

  1. 郑州大学化学与分子工程学院 郑州 450001
  • 收稿日期:2018-09-03 修回日期:2018-10-27 出版日期:2019-04-25 发布日期:2018-12-21
  • 通讯作者: 龙跃 E-mail:longyue@zzu.edu.cn
  • 基金资助:

    国家自然科学基金(No.J1210060)、河南省科技攻关计划(No.0624420031)和河南省基础研究基金(No.022463001)资助项目.

Synthesis and Biological Activities of 1,3,4-Thiadiazole Triazene Compound

Zhang Mingqian, Liu Binkai, Lei Qiang, Yan Jingdong, Zhao Zhongyu, Long Yue   

  1. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001
  • Received:2018-09-03 Revised:2018-10-27 Online:2019-04-25 Published:2018-12-21
  • Contact: 10.6023/cjoc201809003 E-mail:longyue@zzu.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No.J1210060),the Science and Technology Planning Project of Henan Province (No.0624420031) and the Basic Research Development Program of Henan Province (No.022463001).

利用拼接原理将药效基团三氮烯与1,3,4-噻二唑相拼接,合成了15个未见报道的1,3,4-噻二唑三氮烯类衍生物,并用核磁共振波谱(NMR)、红外光谱(IR)和高分辨质谱(HRMS)等方法确定化合物结构.通过以典型三氮烯药物达卡巴嗪(DTIC)和药物5-氟尿嘧啶(5-FU)作参照,对人食管癌细胞(EC109)、人胃癌细胞(MGC803)和人前列腺癌细胞(PC-3)做活性检测,结果显示部分化合物对人胃癌细胞(MGC803)的抑制作用强于达卡巴嗪(DTIC),其中2-(3-甲基苯胺基)-5-[4-(3,3-二甲基三氮烯-1-基)苯基]-1,3,4-噻二唑(8c),2-(2-甲氧基苯胺基)-5-[4-(3,3-二甲基三氮烯-1-基)苯基]-1,3,4-噻二唑(8f),2-(3,4-二氯苯胺基)-5-[4-(3,3-二甲基三氮烯-1-基)苯基]-1,3,4-噻二唑(8l)的IC50值低于5-氟尿嘧啶,分别为5.3,6.5和6.3 μmol/L·部分化合物对人前列腺癌细胞(PC-3)的抑制作用强于达卡巴嗪(DTIC),其中8l的IC50值低于5-氟尿嘧啶,为13.5 μmol/L.

关键词: 三氮烯, 1,3,4-噻二唑, 人食管癌细胞, 人胃癌细胞, 人前列腺癌细胞

Using the splicing principle of combining the pharmacological group triazene with 1,3,4-thiadiazole, 15 unreported 1,3,4-thiadiazole triazene derivatives were synthesized. The structures of the compounds were determined by nucleated magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). By using the typical triazene drug dacarbazine (DTIC) and drug 5-fluorouracil (5-FU) as a reference, the activity detections of human esop-hageal cancer cells (EC109), human gastric cancer cells (MGC803), and human prostate cancer cells (PC-3) were carried out. The results showed that some compounds inhibited human gastric cancer cells (MGC803) more strongly than dacarbazine (DTIC), and the IC50 values of compounds 2-(3-methyanilino)-5-[4-(3,3-dimethyltriazol-1-yl) phenyl]-1,3,4-thiadiazole (8c), 2-(2-methoxyanilino)-5-[4-(3,3-dimethyltriazol-1-yl) phenyl]-1,3,4-thiadiazole (8f), and 2-(3,4-dichloroanilino)-5-[4-(3,3-di-methyltriazol-1-yl) phenyl]-1,3,4-thiadiazole (8l) were lower than those of 5-fluorouracil with 5.3, 6.5 and 6.3 μmol/L, respec-tively. Some compounds inhibited human prostate cancer cells (PC-3) more strongly than dacarbazine (DTIC), and the IC50 value of 8l is lower than that of 5-fluorouracil with 13.5 μmol/L.

Key words: triazene, 1,3,4-thiadiazole, human esophageal cancer cells, human gastric cancer cells, human prostate cancer cells