有机化学 ›› 2015, Vol. 35 ›› Issue (12): 2624-2628.DOI: 10.6023/cjoc201505027 上一篇    下一篇

研究简报

含1,3,4-噻二唑的二硫醚衍生物的合成及抗肿瘤活性研究

李莎, 荆芬, 付小云, 赵继军, 王雪峰, 李宝林, 刘玉明, 陈宝泉   

  1. 天津理工大学化学化工学院 天津 300384
  • 收稿日期:2015-05-16 修回日期:2015-07-12 发布日期:2015-08-31
  • 通讯作者: 陈宝泉 E-mail:chenbaoquan66@126.com
  • 基金资助:

    国家自然科学基金(No. 20971097)和天津市自然科学基金(No. 13JCYBJC24500)资助项目.

Synthesis and Antitumor Activities of Disulfide Derivatives Containing 1,3,4-Thiadiazole Moiety

Li Sha, Jing Fen, Fu Xiaoyun, Zhao Jijun, Wang Xuefeng, Li Baolin, Liu Yuming, Chen Baoquan   

  1. School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384
  • Received:2015-05-16 Revised:2015-07-12 Published:2015-08-31
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 20971097) and the Tianjin Municipal Natural Science Foundation (No. 13JCYBJC24500).

以硫醇、硫脲、2-氨基-5-巯基-1,3,4-噻二唑等为原料, 通过两步反应合成了10个新的含1,3,4-噻二唑的二硫醚衍生物, 并利用IR, 1H NMR, ESI-MS 和元素分析对目标化合物进行了结构表征. 采用CCK-8法测试了目标产物对人体肝癌细胞SMMC-7721, 乳腺癌细胞MCF-7和肺癌细胞A549等肿瘤细胞的增殖抑制活性. 结果表明, 对于不同的肿瘤细胞, 大多数试验化合物显示了较好的增殖抑制活性, 且其活性优于阳性对照药5-氟尿嘧啶. 尤其是正丙基(2-氨基- 1,3,4-噻二唑-5-基)二硫醚(3b)和正丁基(2-氨基-1,3,4-噻二唑-5-基)二硫醚(3d), 对SMMC-7721细胞显示了高效的增殖抑制效果, IC50值分别为1.68和1.93 μmol/L. 4-氯苄基(2-氨基-1,3,4-噻二唑-5-基)二硫醚(3i)对MCF-7细胞表现了显著的抗增殖活性(IC50值为1.78 μmol/L), 且对A549细胞展现了最好的抑制效果(IC50值为4.04 μmol/L).

关键词: 1,3,4-噻二唑, 二硫醚, 合成, 抗肿瘤活性

Ten novel disulfide derivatives containing 1,3,4-thiadiazole moiety were synthesized from appropriate thiols, thiourea and 2-amino-5-mercapto-1,3,4-thiadiazole via two steps reactions. All compounds were characterized by IR, 1H NMR, ESI-MS techniques and elemental analysis. The in vitro antiproliferative activities of target compounds against SMMC-7721 (human liver cancer cell), MCF-7 (human breast cancer cell) and A549 (human lung cancer cell) cells were evaluated by CCK-8 assay. The bioassay results demonstrated that most of the tested compounds showed better antiproliferative activities, and exhibited stronger effects than positive control 5-fluorouracil (5-FU) against various cancer cell lines. Particularly, n-propyl (2-amino-1,3,4-thiadiazol-5-yl)disulfide (3b) and n-butyl (2-amino-1,3,4-thiadiazol-5-yl)disulfide (3d) displayed highly effective antiproliferative effects against SMMC-7721 cells with IC50 values of 1.68 and 1.93 μmol/L. 4-Chlorobenzyl (2-amino-1,3,4-thiadiazol-5-yl)disulfide (3i) exhibited significant antiproliferative activities against MCF-7 cells with IC50 value of 1.78 μmol/L, and revealed the best inhibitory effect against A549 cells with IC50 value of 4.04 μmol/L.

Key words: 1,3,4-thiadiazole, disulfide, synthesis, antitumor activity