Citation: Li Yingjun, Yang Kaidong, Jin Kun, Gao Lixin, Sheng Li, Liu Xuejie, Yang Hongjing, Lin Ledi, Li Jia. Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Carbazole-Based Mono-/Bis-thiocarbohydrazone Derivatives[J]. Chinese Journal of Organic Chemistry, ;2020, 40(1): 162-174. doi: 10.6023/cjoc201905043 shu

Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Carbazole-Based Mono-/Bis-thiocarbohydrazone Derivatives

Li Yingjun ^a,, ,
Yang Kaidong ^a ,
Jin Kun ^b ,
Gao Lixin ^c ,
Sheng Li ^c ,
Liu Xuejie ^a ,
Yang Hongjing ^a ,
Lin Ledi ^a ,
Li Jia ^c,,

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

Corresponding author: Li Yingjun, jli@simm.ac.cn Li Jia, jli@simm.ac.cn
Received Date: 21 May 2019
Revised Date: 2 August 2019
Available Online: 12 January 2019
Fund Project: the Natural Science Foundation of Liaoning Province 20102126Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126)

Figures(10)

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.
- thiocarbohydrazone,
- carbazole,
- synthesis,
- Cdc25B and PTP1B inhibitor,
- molecular docking,
- DFT calculations
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