| 王胜红,韩潇,毛婷,曾慧君,陈瑞,陈慧琼.化学通报,2019,82(7):623-629. |
| 新型四氢苯并[4'',5'']噻吩并[3'',2'':5,6]吡啶并[4,3-d]嘧啶类化合物衍生物的合成及抗肿瘤活性 |
| Synthesis and antitumor activity evaluation of novel tetrahydrobenzo[4 |
| 投稿时间：2019-02-24 修订日期：2019-03-13 |
| DOI： |
| 中文关键词: 氮杂Wittig反应 四氢苯并[4 |
| 英文关键词:Synthesis and Antitumor Activity Evaluation of Novel Tetrahydrobenzo[4'',5'']thieno[3'',2'':5,6]pyrido[4,3-d]pyrimidine Derivatives |
| 基金项目:湖北省普通高等学校人文社会科学重点研究基地湖北技能型人才培养研究中心项目（2018JB009）、2017年度湖北省教育厅科研计划项目（B2017578） |
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| 中文摘要: |
| 目的 设计合成四氢苯并[4'',5'']噻吩并[3'',2'':5,6]吡啶并[4,3-d]嘧啶类化合物并考察其抗肿瘤活性。方法 以环己酮为原料，通过氮杂Wittig反应合成了一系列结构新颖的取代四氢苯并噻吩并吡啶并嘧啶衍生物，并采用MTT法考察所合成目标化合物对CNE2、KB、MGC-803、MCF-7和PC3这五种肿瘤细胞的抑制活性。结果 共合成了25个新化合物，其结构均通过IR、1H NMR、13C NMR和HR-MS进行确认。初步的生物活性结果表明，目标化合物对五种肿瘤细胞均有抑制活性，尤其是对胃癌MGC-803细胞有更强的抑制活性。其中3-(4-氟苯基)-2-((4-氟苯基)氨基)-5-甲基-8,9,10,11-四氢苯并[4'',5'']噻吩并[3'',2'':5,6]吡啶并[4,3-d]嘧啶-4(3H)-酮 [化合物8c, IC50 = (0.9 ± 0.25) umol?L-1]对胃癌细胞MGC-803的抑制活性最强，是5-氟尿嘧啶[IC50 = (18.4 ± 1.43) umol?L-1]的20倍；同时，目标化合物对正常的胃黏膜上皮细胞GES-1没有毒性，而5-氟尿嘧啶有毒性。结论 四氢苯并[4'',5'']噻吩并[3'',2'':5,6]吡啶并[4,3-d]嘧啶类化合物具有良好的抗肿瘤活性，可进行更深入的研究。 |
| 英文摘要: |
| Objective To design and synthesize tetrahydrobenzo[4'',5'']thieno[3'',2'':5,6]pyrido[4,3-d]pyrimidine derivatives and to investigate their anti-tumor activities in vitro. Methods A novel series of tetrahydrobenzo[4'',5'']thieno[3'',2'':5,6]pyrido[4,3-d]pyrimidine derivatives were designed and synthesized via a tandem aza-Wittig reaction, their anti-tumor activities in vitro were evaluated for CNE2, KB, MGC-803, MCF-7 and PC3 cells by MTT assay. Results Twenty-five novel tetrahydrobenzo[4'',5'']thieno[3'',2'':5,6]pyrido[4,3-d]pyrimidine derivatives were synthesized and the structures of compounds prepared were confirmed by the application of IR, 1H NMR, 13C NMR and HR-MS. The preliminary biological results showed that these conjugates displayed significant antiproliferative effect on these five cancer cells, especially for MGC-803. Compound 8c (IC50 = 0.9 ± 0.25 umol?L-1) stood out as the most potent against MGC-803, which was 20-fold more potent than 5-FU (IC50 = 18.4 ± 1.43 umol?L-1). Additionally, all compounds were nontoxic to health GES-1 and VERO cells, while 5-FU showed essential toxicity. Conclusion Tetrahydrobenzo[4'',5''] thieno [3'',2'':5,6] pyrido[4,3-d] pyrimidine compounds displayed promising antitumor activities, which is worth further being developed. |
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