新型含咔唑环芳氨基乙酰腙衍生物的合成及其蛋白酪氨酸磷酸酶1B (PTP1B)抑制活性评价
收稿日期: 2021-02-24
修回日期: 2021-04-02
网络出版日期: 2021-05-14
基金资助
辽宁省自然科学基金(20102126)
Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Arylaminoacetylhydrazone Derivatives Containing Carbazole Moiety
Received date: 2021-02-24
Revised date: 2021-04-02
Online published: 2021-05-14
Supported by
Natural Science Foundation of Liaoning Province(20102126)
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
李英俊 , 林乐弟 , 靳焜 , 高立信 , 盛丽 , 刘季红 , 李佳 . 新型含咔唑环芳氨基乙酰腙衍生物的合成及其蛋白酪氨酸磷酸酶1B (PTP1B)抑制活性评价[J]. 有机化学, 2021 , 41(8) : 3157 -3170 . DOI: 10.6023/cjoc202102046
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.
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