摘要/Abstract

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/mL.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/mL.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
A series of novel carbazole-based mono-/bis-thiocarbohydrazone derivatives were synthesized. Their structures were characterized by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. The inhibitory activities of the target compounds against Cdc25B/PTP1B 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 Cdc25B and PTP1B. Among them, 1,5-bis[(9-pentyl-3-carbazolyl)methylene]thiocarbohydrazone (4d) had the highest inhibitory activity against Cdc25B with IC₅₀=(0.23±0.02) μg/mL, and 1,5-bis[(9-ethyl-3-carbazolyl)methylene]thiocarbohydrazone (4a) had the highest inhibitory activity against PTP1B with IC₅₀=(1.00±0.16) μg/mL. Molecular docking and density functional theory (DFT) calculations of the target compounds 4a and 4d were performed. Molecular docking results indicated that the target compounds 4d and 4a entered the active sites of Cdc25B and PTP1B enzymes, respectively, and thiocarbohydrazone and carbazole groups play the importent role of activity.
Key words: thiocarbohydrazone, carbazole, synthesis, Cdc25B and PTP1B inhibitor, molecular docking, DFT calculations


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