| 基于咔唑的单-/双-硫代碳酰腙衍生物的合成及Cdc25B/PTP1B抑制活性评价 |
| |
| 引用本文： | 李英俊,杨凯栋,靳焜,高立信,盛丽,刘雪洁,杨鸿境,林乐弟,李佳.基于咔唑的单-/双-硫代碳酰腙衍生物的合成及Cdc25B/PTP1B抑制活性评价[J].有机化学,2020(1):162-174. |
| |
| 作者姓名： | 李英俊 杨凯栋 靳焜 高立信 盛丽 刘雪洁 杨鸿境 林乐弟 李佳 |
| |
| 作者单位： | 辽宁师范大学化学化工学院;大连理工大学精细化工国家重点实验室;中国科学院上海药物研究所 |
| |
| 基金项目： | 辽宁省自然科学基金(No.20102126)资助项目。 |
| |
| 摘 要： | 合成了一系列新型的基于咔唑的单-/双-硫代碳酰腙衍生物.利用IR、1H NMR、13C NMR和元素分析对其进行了结构表征.评价了目标化合物对Cdc25B和PTP1B的抑制活性,讨论了其结构与活性的关系.实验结果显示,大部分目标化合物对Cdc25B和PTP1B表现出良好的抑制活性.其中,1,5-双(9-戊基-3-咔唑基)亚甲基]硫代碳酰腙(4d)对Cdc25B的抑制活性最高,IC50为(0.23±0.02)μg/m L.1,5-双(9-乙基-3-咔唑基)亚甲基]硫代碳酰腙(4a)对PTP1B的抑制活性最高, IC50为(1.00±0.16)μg/m L.对目标化合物4a和4d进行分子对接研究和密度泛函理论(DFT)计算,结果表明,目标化合物4d和4a分别进入到了Cdc25B和PTP1B酶的活性位点区域,有活性作用的主要是硫代碳酰腙和咔唑基团.
|
| 关 键 词： | 硫代碳酰腙 咔唑 合成 Cdc25B和PTP1B抑制剂 分子对接 DFT计算 |
Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Carbazole-Based Mono-/Bis-thiocarbohydrazone Derivatives |
| |
| Li Yingjun,Yang Kaidong,Jin Kun,Gao Lixin,Sheng Li,Liu Xuejie,Yang Hongjing,Lin Ledi,Li Jia.Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Carbazole-Based Mono-/Bis-thiocarbohydrazone Derivatives[J].Chinese Journal of Organic Chemistry,2020(1):162-174. |
| |
| Authors: | Li Yingjun Yang Kaidong Jin Kun Gao Lixin Sheng Li Liu Xuejie Yang Hongjing Lin Ledi Li Jia |
| |
| Institution: | (College of Chemistry and Chemical Engineering,Liaoning Normal University,Dalian,Liaoning 116029;State Key Laboratory of Fine Chemicals,Dalian University of Technology,Dalian,Liaoning 116012;National Center for Dmg Screening,State Key Laboratory of Drag Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203) |
| |
| Abstract: | A series of novel carbazole-based mono-/bis-thiocarbohydrazone derivatives were synthesized. Their structures were characterized by IR, 1 H NMR, 13 C NMR spectra and elemental analysis. The inhibitory activities of the target compounds against Cdc25 B/PTP1 B were evaluated, and the relationship between structure and activity was discussed. The results showed that most of the target compounds had good inhibitory activity against Cdc25 B and PTP1 B. Among them, 1,5-bis(9-pentyl-3-carbazolyl)methylene]thiocarbohydrazone(4 d) had the highest inhibitory activity against Cdc25 B with IC50=(0.23±0.02) μg/m L, and 1,5-bis(9-ethyl-3-carbazolyl)methylene]thiocarbohydrazone(4 a) had the highest inhibitory activity against PTP1 B with IC50=(1.00±0.16) μg/m L. Molecular docking and density functional theory(DFT) calculations of the target compounds 4 a and 4 d were performed. Molecular docking results indicated that the target compounds 4 d and 4 a entered the active sites of Cdc25 B and PTP1 B enzymes, respectively, and thiocarbohydrazone and carbazole groups play the importent role of activity. |
| |
| Keywords: | thiocarbohydrazone carbazole synthesis Cdc25B and PTP1B inhibitor molecular docking DFT calculations |
| 本文献已被 CNKI 维普 等数据库收录！ |
|
