摘要/Abstract

为寻找新型蛋白酪氨酸磷酸酶1B (PTP1B)抑制剂, 设计并合成了一系列新型含咔唑环芳氨基乙酰腙衍生物. 其结构和构型用IR、¹H NMR、¹³C NMR和2D NMR(包括¹H-¹H COSY、¹H-¹³C HMBC和NOESY)谱及元素分析进行了确证. 通过对PTP1B抑制活性的测试发现, 目标化合物对PTP1B有较强的抑制作用, 且大多数化合物的IC₅₀值低于阳性对照药物齐墩果酸, 其中N'-(9-辛基咔唑-3-亚甲基)-2-(4-硝基苯氨基)乙酰肼(3t)活性最高, IC₅₀=(2.78±0.04) μmol/L. 利用分子对接研究了化合物3t与PTP1B酶的结合情况.
关键词: 蛋白酪氨酸磷酸酶1B (PTP1B)抑制剂, 咔唑, 芳氨基乙酰腙, 合成, 分子对接
In order to find novel protein tyrosine phosphatase 1B (PTP1B) inhibitors, a series of novel arylaminoacetylhydrazone derivatives containing carbazole moiety were designed and synthesized. Their structures and configurations were confirmed by IR, ¹H NMR, ¹³C NMR, two-dimensional NMR spectra (including ¹H-¹H COSY, ¹H-¹³C HMBC and NOESY) and elemental analysis. The inhibitory activities of all the target compounds against PTP1B were tested, and it was found that the target compounds had potent inhibitory activity against PTP1B, and most of them had lower IC₅₀ value than the positive control drug oleanolic acid. Among them, N'-(9-octylcarbazol-3-ylmethylene)-2-(4-nitrophenylamino)acetohydrazide (3t) had the highest inhibitory activity against PTP1B with IC₅₀ of (2.78±0.04) μmol/L. Molecular docking was used to study the bind of compound 3t with PTP1B enzyme.
Key words: protein tyrosine phosphatase 1B (PTP1B) inhibitor, carbazole, arylaminoacetylhydrazone, synthesis, molecular docking


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