| 刘斯宇,代娇娇,尤晶,王周玉,杨羚羚.化学通报,2018,81(5):456-460. |
| 新型3,5-二取代1H-吲哚衍生物的合成及抗肿瘤活性研究 |
| Synthesis and Anticancer Evaluation of New 3, 5-disubstituted- 1H-indole Derivatives |
| 投稿时间：2017-11-14 修订日期：2018-03-04 |
| DOI： |
| 中文关键词: 肿瘤 吲哚衍生物 胰腺癌 肿瘤细胞 |
| 英文关键词:Tumour, Indole derivatives, Pancreatic cancer, Tumor cell |
| 基金项目:四川省教育厅重点项目(16205459) 、西华大学“西华杯”大学生创新创业项目(2017057) |
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| 中文摘要: |
| 新型抗肿瘤药物研究是全球药物开发的重点任务之一。鉴于前期我们发现3,5-二取代1H-吲哚衍生物具有明显抗胰腺癌活性，本文通过维尔斯迈尔-哈克反应、仲胺的叔丁氧羰基(Boc)保护、醛还原、羧酸与胺的缩合等反应获得了一条高效简洁的3-取代硫甲基-5-酰氨基吲哚衍生物合成路线，并合成了8个全新目标化合物11a-11h。经细胞活性测试发现11a-11h对胰腺癌细胞株BxPC-3均有较好抑制活性，其中11e活性最高(IC50为2.28μmol/L)。对多种肿瘤细胞及人正常肝细胞HL-7702的抑制活性测试表明11e为特异性BxPC-3抑制剂而非细胞毒化合物。鉴于此，11e可能是一个较好的抗胰腺癌苗头化合物，值得进一步深入研究。 |
| 英文摘要: |
| Study on new anticancer drugs is one of the key tasks of global drug development. We previously found that 3,5-disubstituted-1H-indole derivatives have apparent inhibitory activity against pancreatic cancer cells. Here we proposed a new simple and efficient route for the synthesis of 3-((substituted-thio)methyl)- 5-acylamino-1H-indole derivatives, which involves Vilsmeier–Haack reaction, Boc protection of secondary amine, aldehyde reduction, carboxylic acid and amine condensation reaction, and synthesized 8 new target compounds (11a-11h). The cell-based assays revealed that 11a-11h show inhibition to pancreatic cancer cell line BxPC-3; 11e is the most potent compound with an IC50 value of 2.28 μmol/L. 11e was observed to have no/low activity to other tested cancer cell lines and human normal liver cell line HL-7702, indicating that it is not a cytotoxic compounds. Overall, 11e may be a good hit compound for further efforts to develop new inhibitors against pancreatic cancer. |
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