新型5,6-二取代吡啶-2,3-二酮-3-硫代半卡巴腙衍生物作为潜在抗癌剂的设计与合成
Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents.
作者信息
Xie Wenlin, Xie Shimin, Zhou Ying, Tang Xufu, Liu Jian, Yang Wenqian, Qiu Minghua
机构信息
School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, China; Hunan Provincial University Key Laboratory of QSAR/QSPR, China.
Hunan University of Humanities, Science and Technology, Loudi 417000, China.
出版信息
Eur J Med Chem. 2014 Jun 23;81:22-7. doi: 10.1016/j.ejmech.2014.05.001. Epub 2014 May 4.
A series of 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives(2a-2n) and 5,6-disubstituted pyridine-2,3-dione S-benzyl-3-thiosemicarbazones(3a-3g) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and nucleophilic substitutions. The structures of the compounds were established by IR, (1)H NMR, (13)C NMR, and HRMS. All newly synthesized compounds were screened for their anticancer activity against Breast cancer (MCF-7), Colon cancer (HCT-116) and hepatocellular cancer (BEL7402) cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells in vitro. Some of the compounds exhibited promising antiproliferative activity, which were comparable to the positive control (5-fluorouracil). The structure-activity relationship was discussed.
以2,3 - 二羟基吡啶为起始原料，通过氧化 - 迈克尔加成、缩合和亲核取代反应，合成了一系列5,6 - 二取代吡啶 - 2,3 - 二酮 - 3 - 硫代半卡巴腙衍生物（2a - 2n）和5,6 - 二取代吡啶 - 2,3 - 二酮S - 苄基 - 3 - 硫代半卡巴腙（3a - 3g）。通过红外光谱、氢核磁共振谱、碳核磁共振谱和高分辨质谱确定了化合物的结构。对所有新合成的化合物进行了抗乳腺癌（MCF - 7）、结肠癌（HCT - 116）和肝癌（BEL7402）细胞系的抗癌活性筛选。生物测定结果表明，大多数制备的化合物在体外对各种癌细胞表现出细胞毒性。一些化合物表现出有前景的抗增殖活性，与阳性对照（5 - 氟尿嘧啶）相当。讨论了构效关系。
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