Citation: 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]. Chinese Journal of Organic Chemistry, ;2018, 38(5): 1242-1250. doi: 10.6023/cjoc201709022 shu

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

Corresponding author: Li Yingjun, chemlab.lnnu@163.com Li Jian,
Received Date: 13 September 2017
Revised Date: 4 December 2017
Available Online: 3 May 2018
Fund Project: the Natural Science Foundation of Liaoning Province 20102126Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126)

Figures(4)

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.
- acylthiourea,
- carbazole,
- synthesis,
- Cdc25B and PTP1B inhibitors,
- molecular docking
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