Citation: LI Yingjun, YANG Hongjing, CAO Xin, GAO Lixin, JIN Kun, SHENG Li, LIU Jihong, LIU Xuejie, LI Jia. Synthesis of 3, 6-Disubstituted Triazolothiadiazole Derivatives and Their Inhibitory Activities Against Cell Division Cycle 25B Phosphatase and Protein Tyrosine Phosphatase 1B[J]. Chinese Journal of Applied Chemistry, ;2020, 37(9): 994-1002. doi: 10.11944/j.issn.1000-0518.2020.09.200040 shu

Synthesis of 3, 6-Disubstituted Triazolothiadiazole Derivatives and Their Inhibitory Activities Against Cell Division Cycle 25B Phosphatase and Protein Tyrosine Phosphatase 1B

LI Yingjun ^a,, ,
YANG Hongjing ^a ,
CAO Xin ^a ,
GAO Lixin ^b ,
JIN Kun ^c ,
SHENG Li ^b ,
LIU Jihong ^d ,
LIU Xuejie ^a ,
LI Jia ^b,,

a.
College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, Liaoning 116029, China
b.
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
c.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, Liaoning 116012, China
d.
Chemistry Analysis and Inspection Center, Dalian University of Technology, Dalian, Liaoning 116023, China

Corresponding author: LI Yingjun, chemlab.lnnu@163.com LI Jia, jli@simm.ac.cn
Received Date: 16 February 2020
Revised Date: 13 April 2020
Accepted Date: 5 June 2020

Fund Project: Natural Science Foundation of Liaoning Province No.20102126Supported by the Natural Science Foundation of Liaoning Province(No.20102126)

Figures(2)

A series of 3, 6-disubstituted triazolothiadiazole derivatives 3a-3l containing benzimidazole/aryloxymethyl scaffolds was synthesized. Their structures were confirmed by Fourier transform infrared spectrometry (FT-IR), nuclear magnetic resonance spectroscopy (NMR) and elemental analysis. The inhibitory activity of all synthesized target compounds against cell division cycle 25B phosphatase (Cdc25B)/protein tyrosine phosphatase 1B (PTP1B) was evaluated, and the structure-activity relationship was discussed. The bioassay results show that target compound 3a has the highest inhibitory activity against Cdc25B and PTP1B with the half inhibitory concentration (IC₅₀) values of (0.46±0.02) μg/mL and (1.77±0.40) μg/mL, respectively. The obtained research results provide a reference for the development of novel Cdc25B/PTP1B inhibitors.
- triazolothiadiazole,
- benzimidazole,
- aryloxyacetic acid,
- cell division cycle 25B phosphatase inhibitor,
- protein tyrosine phosphatase 1B inhibitor
1. [1]
  Ramaprasad G C, Kalluraya B, Kumar B S. Microwave-assisted of Triazolothiadiazole Analogs as Anticancer Agents[J]. Med Chem Res, 2014,23:3644-3651. doi: 10.1007/s00044-014-0944-x
2. [2]
  Jubie S, Bincy B, Begam A J. A New Class of Human Fatty Acid Synthase Inhibitors:Synthesis and Their Anticancer Evaluation[J]. Indian J Chem, 2018,57B:671-678.
3. [3]
  Liu X J, Liu H Y, Wang H X. Synthesis and Antitumor Evaluation of Novel Fused Heterocyclic 1, 2, 4-Triazolo[3, 4-b]-1, 3, 4-Thiadiazole Derivatives[J]. Med Chem Res, 2019,28(10):1718-1725. doi: 10.1007/s00044-019-02409-2
4. [4]
  Joshi H H, Parsania M V. Synthesis, Characterization 3-(5-Bromothiophen-2-yl)-6-Phenyl-1, 7a-Dihydro-[1, 2, 4] triazolo[3, 4-b] [1, 3, 4] thiadiazole Derivatives and Biological Property[J]. World Sci News, 2019,126:291-297.
5. [5]
  Asma K B, Manju N, Chandra M M. Synthesis, Antimicrobial, Antioxidant and Molecular Docking Study of Some Novel Bis-1, 2, 4-Triazolo[3, 4-B]-1, 3, 4-Thiadiazoles[J]. J Med Chem Drug Des, 2018,1(1):1-6.
6. [6]
  Ahmed M S, Essa H J, Khan A K. Synthesis, Characterization and Preliminary Pharmacological Evaluation of Triazolothiadiazoles Derived from Some NSAIDs and Thiocarbohydrazide[J]. Al-Mustansiriyah J Pharm Sci, 2018,18(1):73-92.
7. [7]
  Deng Q, Meng J, Liu Y. IMB-SD62, A Triazolothiadiazoles Derivative with Promising Action Against Tuberculosis[J]. Tuberculosis, 2018,112:37-44. doi: 10.1016/j.tube.2018.07.006
8. [8]
  Sarafroz M, Khatoon Y, Ahmad N. Synthesis, Characterization and Anticonvulsant Activity of Novel Fused 1, 2, 4-Triazolo-1, 3, 4-Thiadiazoles[J]. Orient J Chem, 2019,35(1):64-70. doi: 10.13005/ojc/350107
9. [9]
  Hiremathad A, Piemontese L. Heterocyclic Compounds as Key Structures for the Interaction with Old and New Targets in Alzheimer's Disease Therapy[J]. Neural Regener Res, 2017,12(8):1256-1261. doi: 10.4103/1673-5374.213541
10. [10]
11. [11]
  Dennie T W, Kolesar J M. Bendamustine for the treatment of Chronic Lymphocytic Leukemia and Rituximab-Refractory, Indolent B-Cell Non-hodgkin Lymphoma[J]. Clin Ther, 2009,31:2290-2311. doi: 10.1016/j.clinthera.2009.11.031
12. [12]
  Özil M, Emirik M, Etlik S Y. A Simple and Efficient Synthesis of Novel Inhibitors of alpha-Glucosidase Based on Benzimidazole Skeleton and Molecular Docking Studies[J]. Bioorg Chem, 2016,68:226-235. doi: 10.1016/j.bioorg.2016.08.011
13. [13]
  Mahmoud M A, Redayan M A. Synthesis, Characterization, and Antibacterial Screening of Some New Benzimidazole Derivatives Having 1, 3, 4-Thiadiazole Ring[J]. Int J Pharm Res, 2019,11(3):247-251.
14. [14]
  Kashid B B, Ghanwat A A, Khedkar V M. Design, Synthesis, in vitro Antimicrobial, Antioxidant Evaluation, and Molecular Docking Study of Novel Benzimidazole and Benzoxazole Derivatives[J]. J Heterocycl Chem, 2019,56(3):895-908. doi: 10.1002/jhet.3467
15. [15]
  Sethi P, Bansal Y, Bansal G. Synthesis and PASS-assisted Evaluation of Coumarin Benzimidazole Derivatives as Potential Anti-inflammatory and Anthelmintic Agents[J]. Med Chem Res, 2018,27(1):61-71.
16. [16]
  Begum S, Bharathi K, Prasad K. Mini Review on Therapeutic Profile of Phenoxy Acids and Thier Derivatives[J]. Int J Pharm Pharm Sci, 2016,8(10):66-71. doi: 10.22159/ijpps.2016v8i10.5005
17. [17]
  Lee K, Lee J H, Boovanahalli S K. (Aryloxyacetylamino)benzoic Acid Analogues:A New Class of Hypoxia-Inducible Factor-1 Inhibitors[J]. J Med Chem, 2007,50(7):1675-1684. doi: 10.1021/jm0610292
18. [18]
  Liu H, Sun D, Du H. Synthesis and Biological Evaluation of Tryptophan-Derived Rhodanine Derivatives as PTP1B Inhibitors and Anti-bacterial Agents[J]. Eur J Med Chem, 2019,172:163-173. doi: 10.1016/j.ejmech.2019.03.059
19. [19]
  He R, Yu Z, Zhang R. Protein Tyrosine Phosphatases as Potential Therapeutic Targets[J]. Acta Pharmacol Sin, 2014,35(10):1227-1246. doi: 10.1038/aps.2014.80
20. [20]
  Kostrzewa T, Styszko J, Gorska-Ponikowska M. Inhibitors of Protein Tyrosine Phosphatase PTP1B with Anticancer Potential[J]. Anticancer Res, 2019,39(7):3379-3384. doi: 10.21873/anticanres.13481
21. [21]
  Lazo J S, McQueeney K E, Burnett J C. Small Molecule Targeting of PTPs in Cancer[J]. Int J Biochem Cell Biol, 2018,96:171-181. doi: 10.1016/j.biocel.2017.09.011
22. [22]
  Li Y, Yu Y, Jin K. Synthesis and Biological Evaluation of Novel Thiadiazole Amides as Potent Cdc25B and PTP1B Inhibitors[J]. Bioorg Med Chem Lett, 2014,24(17):4125-4128. doi: 10.1016/j.bmcl.2014.07.055
23. [23]
  Ha G S, Lee C M, Kim C. Development of a Novel Nonradioisotopic Assay and Cdc25B Overexpression Cell Lines for Use in Screening for Cdc25B Inhibitors[J]. Yonsei Med J, 2018,59(8):995-1003. doi: 10.3349/ymj.2018.59.8.995
24. [24]
  Ma Y, Li H L, Chen X B. 3D QSAR Pharmacophore Based Virtual Screening for Identification of Potential Inhibitors for CDC25B[J]. Comput Biol Chem, 2018,73:1-12. doi: 10.1016/j.compbiolchem.2018.01.005
25. [25]
  Evain-Bana E, Schiavo L, Bour C. Synthesis, Biological Evaluation and Molecular Modeling Studies on Novel Quinonoid Inhibitors of CDC25 Phosphatases[J]. J Enzym Inhib Med Chem, 2017,32(1):113-118. doi: 10.1080/14756366.2016.1238364
26. [26]
  Paudel P, Seong S H, Park H J. Anti-Diabetic Activity of 2, 3, 6-Tribromo-4, 5-Dihydroxybenzyl Derivatives from Symphyocladia latiuscula Through PTP1B Downregulation and α-Glucosidase Inhibition[J]. Mar Drugs, 2019,17(3):166-184. doi: 10.3390/md17030166
27. [27]
  LI Yingjun, LI Jiyang, PENG Lina. Synthesis and Cell Division Cycle 25B Phosphatase and Protein Tyrosine Phosphatase 1B Inhibitory Activity Evaluation of Novel 3, 6-Disubstituted Triazolothiadiazole Derivatives[J]. Chinese J Org Chem, 2017,37(2):485-495.
28. [28]
  LI Yingjun, LIU Lijun, JIN Kun. Synthesis and Biological Activity of Novel 3, 6-Disubstituted 1, 2, 4-Triazolo[3, 4-b]-1, 3, 4-thiadiazoles[J]. Acta Chim Sin, 2010,68(16):1577-1584.
29. [29]
  Baburajeev C P, Mohan C D, Ananda H. Development of Novel Triazolo-Thiadiazoles from Heterogeneous "Green" Catalysis as Protein Tyrosine Phosphatase 1B Inhibitors[J]. Sci Rep, 2015,5(1):14195-14205. doi: 10.1038/srep14195
30. [30]
  LI Yingjun, LIU Lijun, XU Yongting. Study on Nuclear Magnetic Resonance of 4-Amino-5-[2-(4-chlorophenoxymethyl)benzimidazole-1-methylene]-1, 2, 4-triazole-3-thione[J]. Chinese J Anal Chem, 2011,39(6):902-905.
31. [31]
  LI Yingjun, FU Xingji, XU Yongting. Syntheses of Aryloxy (Arylthio) Carboxylic Acids in Solid-Liquid Phase under Supersonic Radiation[J]. Chinese J Appl Chem, 1993,10(6):97-98.
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