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

doi:10.6023/cjoc201905043

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (1): 162-174.DOI: 10.6023/cjoc201905043 Previous Articles Next Articles

基于咔唑的单-/双-硫代碳酰腙衍生物的合成及Cdc25B/PTP1B抑制活性评价

李英俊^a, 杨凯栋^a, 靳焜^b, 高立信^c, 盛丽^c, 刘雪洁^a, 杨鸿境^a, 林乐弟^a, 李佳^c

a 辽宁师范大学化学化工学院辽宁大连 116029;
b 大连理工大学精细化工国家重点实验室辽宁大连 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:2019-05-21 修回日期:2019-08-02 发布日期:2019-09-12
通讯作者: 李英俊, 李佳 E-mail:chemlab.lnnu@163.com;jli@simm.ac.cn
基金资助:
辽宁省自然科学基金（No.20102126）资助项目.

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

Received:2019-05-21 Revised:2019-08-02 Published:2019-09-12
Supported by:
Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

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Abstract

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.

Key words: thiocarbohydrazone, carbazole, synthesis, Cdc25B and PTP1B inhibitor, molecular docking, DFT calculations

Cite this article

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.

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基于咔唑的单-/双-硫代碳酰腙衍生物的合成及Cdc25B/PTP1B抑制活性评价

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

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