Synthesis and Cell Division Cycle 25B Phosphatase/Protein Tyrosine Phosphatase 1B Inhibitory Activity Evaluation of Novel Acylthiourea Derivatives

doi:10.6023/cjoc201709022

Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (5): 1242-1250.DOI: 10.6023/cjoc201709022 Previous Articles Next Articles

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新型酰基硫脲衍生物的合成及细胞分裂周期25B磷酸酶和蛋白酪氨酸磷酸酶1B抑制活性研究

李英俊^a, 王思远^a, 靳焜^b, 高立信^c, 盛丽^c, 张楠^a, 杨凯栋^a, 赵月^a, 李佳^c

a 辽宁师范大学化学化工学院大连 116029;
b 大连理工大学精细化工国家重点实验室大连 116012;
c 中国科学院上海药物研究所国家新药筛选中心药物研究国家重点实验室上海 201203

收稿日期:2017-09-13 修回日期:2017-12-04 发布日期:2018-01-03
通讯作者: 李英俊,E-mail:chemlab.lnnu@163.com E-mail:chemlab.lnnu@163.com
基金资助:
辽宁省自然科学基金（No.20102126）资助项目.

Synthesis and Cell Division Cycle 25B Phosphatase/Protein Tyrosine Phosphatase 1B Inhibitory Activity Evaluation of Novel Acylthiourea Derivatives

Li Yingjun^a, Wang Siyuan^a, Jin Kun^b, Gao Lixin^c, Sheng Li^c, Zhang Nan^a, Yang Kaidong^a, Zhao Yue^a, Li Jian^c

a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012;
c State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203

Received:2017-09-13 Revised:2017-12-04 Published:2018-01-03
Contact: 10.6023/cjoc201709022 E-mail:chemlab.lnnu@163.com
Supported by:
Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

1. Synthesis and Cell Division Cycle 25B Phosphatase/Protein Tyrosine Phosphatase 1B Inhibitory Activity Evaluation of Novel Acylthiourea Derivatives.PDF(1944KB)

Abstract

A series of new acylthiourea derivatives 3 containing carbazole moity have been synthesized by the techniques of ultrasonic irradiation and solid-liquid phase transfer catalysis. Their structures were characterized by IR, ¹H NMR, ¹³C NMR spectra and elemental analysis. This synthetic method has the advantages of short reaction time, simple operation and high yield. All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25B phosphatase (Cdc25B) and protein tyrosine phosphatase 1B (PTP1B). The results show that all the compounds 3 display significant inhibitory activities against Cdc25B, and partial target compounds 3 also show significant inhibitory activities against PTP1B. Among them, 1-(4-nitrobenzoyl)-3-(9-ethyl-carbazole-3-yl)thiourea (3n) exhibits highest inhibitory activity against Cdc25B [IC₅₀=(0.49±0.12) mg/mL] and 1-(2-nitrobenzoyl)-3-(9-ethyl-carbazole-3-yl)thiourea (3l) displays highest inhibitory activity against PTP1B [IC₅₀=(3.59±1.15) mg/mL]. It is noteworthy that compound 3n shows higher inhibitory activity against Cdc25B and PTP1B. The preliminary research results of molecular docking revealed the structural-activity of the inhibitors. The active compounds can be considered as potential Cdc25B and PTP1B inhibitors, and have great application prospects in the treatment of cancers and diabetes.

Key words: acylthiourea, carbazole, synthesis, Cdc25B and PTP1B inhibitors, molecular docking

Cite this article

Li Yingjun, Wang Siyuan, Jin Kun, Gao Lixin, Sheng Li, Zhang Nan, Yang Kaidong, Zhao Yue, Li Jian. Synthesis and Cell Division Cycle 25B Phosphatase/Protein Tyrosine Phosphatase 1B Inhibitory Activity Evaluation of Novel Acylthiourea Derivatives[J]. Chin. J. Org. Chem., 2018, 38(5): 1242-1250.

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新型酰基硫脲衍生物的合成及细胞分裂周期25B磷酸酶和蛋白酪氨酸磷酸酶1B抑制活性研究

Synthesis and Cell Division Cycle 25B Phosphatase/Protein Tyrosine Phosphatase 1B Inhibitory Activity Evaluation of Novel Acylthiourea Derivatives

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