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Volume 22, Issue 3
  • ISSN: 1570-1794
  • E-ISSN: 1875-6271

Abstract

Background

A direct synthesis of functionalized dimethyl fumarate derivatives of 2- (2-(()-(2-oxoindolin-3-ylidene)methyl)-1-benzo[d]imidazol-1-yl) is achieved one-pot reaction involving 2-methyl-1-benzo[]imidazole and appropriate isatin in the presence of DMAD.

Methods

Conversely, this one-pot reaction furnished, upon conduction at 60 ℃, the 2-(2-(()- (2-oxoindolin-3-ylidene)methyl)-1-benzo[d]imidazol-1-yl) products. The biological activities were evaluated against JNK3 kinase. We chose to dock the compounds into the JNK3 binding site in order to comprehend the molecular underpinnings of the observed bioactivities.

Results

The structures of the synthesized compound adduct were evidenced from NMR and MS spectral data and further confirmed by single-crystal X-ray diffraction. The biological activities revealing that the introduction of an alkyl group at the 1-position of the isatin moiety produced JNK3 inhibitors with IC values in the low micromolar range.

Conclusion

This study synthesized a unique compound using a three-component method. Compound showed high antitumor activity (IC = 6.5 µM) against JNK3 inhibitors, while compounds , , and exhibited high selectivity. The research highlights the effectiveness of the one-pot reaction in creating medically useful hybrid compounds, marking a significant advance in medicinal chemistry.

© 2025 Bentham Science Publishers
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2024-09-20
2025-05-12

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References

  1. HammoudaM. FordA. LiuY. ZhangJ. The JNK signaling pathway in inflammatory skin disorders and cancer.Cells20209485710.3390/cells904085732252279
     [Google Scholar]
  2. BarrR.K. BogoyevitchM.A. The c-Jun N-terminal protein kinase family of mitogen-activated protein kinases (JNK MAPKs).Int. J. Biochem. Cell Biol.200133111047106310.1016/S1357‑2725(01)00093‑011551821
     [Google Scholar]
  3. WinS. ThanT.A. ZhangJ. OoC. MinR.W.M. KaplowitzN. New insights into the role and mechanism of c‐Jun‐N‐terminal kinase signaling in the pathobiology of liver diseases.Hepatology20186752013202410.1002/hep.2968929194686
     [Google Scholar]
  4. OhY. JangM. ChoH. YangS. ImD. MoonH. HahJ.M. Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1 H- pyrazole derivatives as a novel selective inhibitor scaffold of JNK3.J. Enzyme Inhib. Med. Chem.202035137237610.1080/14756366.2019.170529431856610
     [Google Scholar]
  5. MusiC.A. AgròG. SantarellaF. IervasiE. BorselloT. JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases.Cells2020910219010.3390/cells910219032998477
     [Google Scholar]
  6. KallunkiT. JNK Subfamily.Encyclopedia of Cancer. SchwabM. Berlin, HeidelbergSpringer Berlin Heidelberg20111927192810.1007/978‑3‑642‑16483‑5_3184
     [Google Scholar]
  7. SolasM. VelaS. SmerdouC. MartisovaE. Martínez-ValbuenaI. LuquinM.R. RamírezM.J. JNK Activation in Alzheimer’s Disease Is Driven by Amyloid β and Is Associated with Tau Pathology.ACS Chem. Neurosci.2023148acschemneuro.3c0009310.1021/acschemneuro.3c0009336976903
     [Google Scholar]
  8. QinP. RanY. LiuY. WeiC. LuanX. NiuH. PengJ. SunJ. WuJ. Recent advances of small molecule JNK3 inhibitors for Alzheimer’s disease.Bioorg. Chem.202212810609010.1016/j.bioorg.2022.10609035964505
     [Google Scholar]
  9. DavisR.J. Signal transduction by the JNK group of MAP kinases.Cell2000103223925210.1016/S0092‑8674(00)00116‑111057897
     [Google Scholar]
  10. WuQ. WuW. JacevicV. FrancaT.C.C. WangX. KucaK. Selective inhibitors for JNK signalling: A potential targeted therapy in cancer.J. Enzyme Inhib. Med. Chem.202035157458310.1080/14756366.2020.172001331994958
     [Google Scholar]
  11. JaberA.M. Al-MahadeenM.M. Al-QawasmehR.A. TahaM.O. Synthesis, anticancer evaluation and docking studies of novel adamantanyl-1,3,4-oxadiazol hybrid compounds as Aurora-A kinase inhibitors.Med. Chem. Res.202332112394240410.1007/s00044‑023‑03145‑4
     [Google Scholar]
  12. JaberA.M. ZahraJ.A. El-AbadelahM.M. SabriS.S. SabbahD.S. Thermodynamic control synthesis of spiro[oxindole-3,3′-pyrrolines] via 1,4-dipolar cycloaddition utilizing imidazo[1,5- a ]quinoline.Z. Naturforsch. C J. Biosci.2023783-414114810.1515/znc‑2022‑008536796786
     [Google Scholar]
  13. Al-MahadeenM.M. JaberA.M. Al-NajjarB.O. Design, synthesis and biological evaluation of novel 2-hydroxy-1 H-indene-1,3(2 H)-dione derivatives as FGFR1 inhibitors.Pharmacia2024711910.3897/pharmacia.71.e122127
     [Google Scholar]
  14. Al-MahadeenM.M. JaberA.M. Al-QawasmehR.A. TahaM.O. Synthesis, evaluation, and docking study of adamantyl-1,3,4-oxadiazol hybrid compounds as CaMKIIδ kinase inhibitor.J. Chem. Res.20244831747519824126246710.1177/17475198241262467
     [Google Scholar]
  15. Jaber, M.A., A.J. Zahra, M.M. El-Abadelah, M.M. Al-Mahadeen, S.S. Sabri, V. Kasabri, and N.R. Haddadin, Evaluation of Spirooxindole- 3,3'-pyrrolines-incorporating Isoquinoline Motif as Antitumor, Anti-Inflammatory, Antibacterial, Antifungal, and Antioxidant Agents.Anti-Inflamm. Anti-Allergy Agents Med. Chem. 2024; 23: p. 1-12.10.2174/0118715230322113240705071750
     [Google Scholar]
  16. Al-MahadeenM.M. ZahraJ.A. El-AbadelahM.M. JaberA.M. KhanfarM.A. One-pot synthesis of novel 2-oxo(2H)-spiro[benzofuran-3,3′-pyrrolines] via 1,4-dipolar cycloaddition reaction.Results Chem2022410064310.1016/j.rechem.2022.100643
     [Google Scholar]
  17. JaberA.M. ZahraJ.A. El-AbadelahM.M. SabriS.S. KhanfarM.A. VoelterW. Utilization of 1-phenylimidazo[1,5- a ]quinoline as partner in 1,4-dipolar cycloaddition reactions.Z. Naturforsch. B. J. Chem. Sci.202075325926710.1515/znb‑2019‑0150
     [Google Scholar]
  18. JaberA.M. ZahraJ.A. SabriS.S. KhanfarM.A. AwwadiF.F. El-AbadelahM.M. New Trends in 1,4-Dipolar Cycloaddition Reactions. Thermodynamic Control Synthesis of Model 2′-(isoquinolin-1-yl)-spiro[oxindole-3,3′-pyrrolines].Curr. Org. Chem.202226554254910.2174/1385272826666220221141306
     [Google Scholar]
  19. Al-MahadeenM.M. JaberA.M. ZahraJ.A. El-AbadelahM.M. AlshaerW. TahaM.O. Synthesis of novel benzothieno-[3,2′-f][1,3] oxazepines and their isomeric 2-oxo-2H-spiro[benzothiophene-3,3′-pyrrolines] via 1,4-dipolar cycloaddition reaction and their evaluation as cytotoxic anticancer leads.Med. Chem. Res.202433691892910.1007/s00044‑024‑03229‑9
     [Google Scholar]
  20. SheldrickG.J.A.C. Synthesis, Characterization and Crystal Structure of a New Schiff Base Ligand from a Bis(Thiazoline) Template and Hydrolytic Cleavage of the Imine Bond Induced by a Co(II) Cation.Open J. Inorg. Chem.2016611665810
     [Google Scholar]
  21. SheldrickG.J.J.A.C. Synthesis, Characterization and Crystal Structure of Cobalt(II) Complex of a Schiff Base Derived from Isoniazid and Pyridine-4-Carboxaldehyde.Cryst. Struct. Theory Appl.2019842645918
     [Google Scholar]
  22. SwahnB.M. HuertaF. KallinE. MalmströmJ. WeigeltT. ViklundJ. WomackP. XueY. ÖhbergL. Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3.Bioorg. Med. Chem. Lett.200515225095509910.1016/j.bmcl.2005.06.08316140012
     [Google Scholar]
  23. MorrisG.M. HueyR. LindstromW. SannerM.F. BelewR.K. GoodsellD.S. OlsonA.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.J. Comput. Chem.200930162785279110.1002/jcc.2125619399780
     [Google Scholar]
  24. Sahar JaffalS.O. Effect of Arbutus andrachne L. methanolic leaf extract on TRPV1 function: Experimental and molecular docking studies.JAPS20221210069077
     [Google Scholar]
  25. Al-AnaziM. KhairuddeanM. Al-NajjarB.O. Murwih AlidmatM. KamalN. MuhamadM. Synthesis, anticancer activity and docking studies of pyrazoline and pyrimidine derivatives as potential epidermal growth factor receptor (EGFR) inhibitors.Arab. J. Chem.202215710386410.1016/j.arabjc.2022.103864
     [Google Scholar]
  26. Dassault-SystèmesBiovia, discovery studio modeling environment.San Diego, CA, USADassault Systèmes Biovia2016
     [Google Scholar]
  27. HevenerK.E. ZhaoW. BallD.M. BabaogluK. QiJ. WhiteS.W. LeeR.E. Validation of molecular docking programs for virtual screening against dihydropteroate synthase.J. Chem. Inf. Model.200949244446010.1021/ci800293n19434845
     [Google Scholar]
/content/journals/cos/10.2174/0115701794335274240910111137
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Novel N-substituted Isatin-oxoindolin-1H-Benzo[D] Imidazole Fumarate as a New Class of JNK3 Inhibitor: Design, Synthesis, Molecular Modeling and its Biological Activity
Curr. Org. Synth. 22, 410 (2025); https://doi.org/10.2174/0115701794335274240910111137
/content/journals/cos/10.2174/0115701794335274240910111137
/content/journals/cos/10.2174/0115701794335274240910111137
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  • Article Type:     Research Article
Keyword(s): 1,3-dipolarcycloaddition; hydrazones; Hydrazonoyl; methylhydrazonecarbodithioates; nitrilimines; thiadiazoles

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