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
收稿日期: 2015-05-16
修回日期: 2015-07-12
网络出版日期: 2015-08-31
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
Received date: 2015-05-16
Revised date: 2015-07-12
Online 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).
李莎 , 荆芬 , 付小云 , 赵继军 , 王雪峰 , 李宝林 , 刘玉明 , 陈宝泉 . 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[J]. 有机化学, 2015 , 35(12) : 2624 -2628 . DOI: 10.6023/cjoc201505027
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
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