新型2,5-二取代-1,3,4-噻二唑衍生物的合成与生物活性
收稿日期: 2014-05-12
修回日期: 2014-08-01
网络出版日期: 2014-09-25
基金资助
辽宁省自然科学基金(No. 20102126)资助项目.
Synthesis and Biological Activities of Novel 2,5-Disubstituted- 1,3,4-thiadiazole Derivatives
Received date: 2014-05-12
Revised date: 2014-08-01
Online published: 2014-09-25
Supported by
Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).
将自行合成的重要中间体2-氨基-5-取代-1,3,4-噻二唑(2)和2-氯硒基苯甲酰氯(6)反应, 合成出了16个新颖的含苯并异硒唑酮结构的2,5-二取代-1,3,4-噻二唑衍生物7a～7p, 利用IR, 1H NMR和元素分析对目标产物进行了结构表征. 评价了目标化合物的生物活性. 实验结果表明, 部分化合物具有抑制细胞分裂周期25 B磷酸酯酶(Cdc25B)的活性 (IC50=1.67～6.66 mmol·L-1). 所有化合物对蛋白酪氨酸磷酸酯酶1B (PTP1B)均有抑制活性(IC50=0.73～4.50 mmol·L-1), 并且部分化合物的抑制活性高于阳性对照药物齐墩果酸(IC50=1.90 mmol·L-1). 化合物7k对人结肠癌(HCT-8)细胞具有体外抗肿瘤活性(IC50=12.54 mmol·L-1). 部分化合物对羟自由基(HO·)和超氧阴离子(O2·-)具有中等的清除能力, 但对DPPH·均无清除能力.
关键词： 2,5-二取代-1,3,4-噻二唑; 苯并异硒唑酮; 合成; 生物活性
李英俊 , 于洋 , 靳焜 , 高立信 , 罗潼川 , 盛丽 , 邵昕 , 李佳 . 新型2,5-二取代-1,3,4-噻二唑衍生物的合成与生物活性[J]. 有机化学, 2015 , 35(1) : 129 -136 . DOI: 10.6023/cjoc201405020
Sixteen novel 2,5-disubstituted-1,3,4-thiadiazole derivatives containing benzisoselenazolone moiety 7a～7p were synthesized by the reaction of 2-amino-5-substituted-1,3,4-thiadiazoles (2) with ortho-(chloroseleno)benzoyl chloride (6). The structures were characterized by IR, 1H NMR spectra and elemental analysis. Their biological activities were evaluated. The experimental results indicate that some compounds exhibit inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) (IC50=1.67～6.66 mmol·L-1). All the target compounds showed good inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) (IC50=0.73～4.50 mmol·L-1), and some compounds exhibited higher inhibitory activity than positive control oleanolic acid (IC50=1.90 mmol·L-1). Compound 7k displayed antitumor activity in vitro for human colon cancer (HCT-8) cell (IC50=12.54 mmol·L-1). Some compounds showed the medium scavenging ability for hydroxyl radical (HO·) and superoxide anion (O2·-), but no scavenging ability for DPPH·.
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