Skip to content
2000
image of Synthesis, Computational Analysis, and Pharmacological Evaluation of Novel Schiff Base Hybrids for Anxiolytic and Skeletal Muscle-Relaxant Activities

Abstract

Introduction

Schiff bases are a well-known class of substances with a variety of pharmacological properties, including skeletal muscle relaxant and anxiolytic effects. They are ideal candidates for the development of CNS-active drugs due to their structural adaptability and ability to interact with a range of biological targets.

The purpose of this study was to create, synthesize, and describe new Schiff base hybrids and assess their possible skeletal muscle relaxant and anxiolytic effects using pharmacological and computational techniques.

Methods

By using condensation reactions between primary amines and substituted aromatic aldehydes, several new Schiff base hybrids were created. FT-IR, 1H NMR, 13C NMR, and mass spectrometry were used for structural elucidation. To evaluate binding affinity with GABA-A and NMDA receptor sites, computational investigations involving molecular docking and ADME profiling were carried out. Validated rodent models were utilized for pharmacological evaluations, including the rotarod and traction tests to assess skeletal muscle relaxation, as well as the elevated plus maze and open-field tests to evaluate anxiolytic activity.

Results

The synthesized Schiff base derivatives demonstrated high purity and stability. In accordance with the observed anxiolytic activity, docking studies demonstrated advantageous binding interactions with the GABA-A receptor.

Discussion

Certain compounds exhibited moderate skeletal muscle relaxant activity, without producing noticeable sedation or motor impairment, as well as significant anxiolytic effects comparable to those of diazepam (p < 0.05). Good drug-likeness and CNS permeability were predicted for the lead compounds by ADME analysis.

Conclusion

Both and tests support the encouraging skeletal muscle relaxant and anxiolytic properties of the synthesized Schiff base hybrids. These results suggest their potential as top contenders for the development of innovative CNS-active medications.

Loading

Article metrics loading...

/content/journals/cnsamc/10.2174/0118715249355436250806100850
2025-09-11
2025-10-18
Loading full text...

Full text loading...

References

  1. Rao D.P. Schiff bases and their possible therapeutic applications: A review. Results Chem. 2024 101941 10.1016/j.rechem.2024.101941
    [Google Scholar]
  2. Mushtaq, Irfan Pharmaceutical significance of Schiff bases: An overview. Futur J. Pharm. Sci. 2024 10 16 10.1186/s43094‑024‑00594‑5
    [Google Scholar]
  3. Boulechfar C. Ferkous H. Delimi A. Djedouani A. Kahlouche A. Boublia A. Darwish A.S. Lemaoui T. Verma R. Benguerba Y. Schiff bases and their metal Complexes: A review on the history, synthesis, and applications. Inorg. Chem. Commun. 2023 150 110451 10.1016/j.inoche.2023.110451
    [Google Scholar]
  4. Tsacheva, Ivelina Pharmacological activities of Schiff bases and their derivatives with low and high molecular phosphonates. Pharmaceuticals 2023 16 7 938 10.3390/ph16070938 37513849
    [Google Scholar]
  5. Ceramella J. A review on the antimicrobial activity of Schiff bases: Data collection and recent studies. Antibiotics 2022 11 2 10.3390/antibiotics11020191 35203793
    [Google Scholar]
  6. Sinicropi, Maria Stefania Metal complexes with Schiff bases: Data collection and recent studies on biological activities. Int. J. Mol. Sci. 2022 23 23 14840 10.3390/ijms232314840 36499170
    [Google Scholar]
  7. Zúñiga-Miranda, Johana Experimental and computational studies of Schiff bases derived from 4-aminoantipyrine as potential antibacterial and anticancer agents. Discov Appl. Sci. 2025 7 115 10.1007/s42452‑025‑06459‑7
    [Google Scholar]
  8. Ahmed Y.M. Elgendi M.A. Omar M.M. Mohamed G.G. Deghadi R.G. Synthesis, characterization, antimicrobial, antioxidant studies, molecular docking and DFT calculations of novel Schiff base and its metal complexes. J. Mol. Struct. 2025 1326 141076 10.1016/j.molstruc.2024.141076
    [Google Scholar]
  9. Kaushik S. Paliwal S.K. Iyer M.R. Patil V.M. Promising Schiff bases in antiviral drug design and discovery. Med. Chem. Res. 2023 32 6 1063 1076 10.1007/s00044‑023‑03068‑0 37305208
    [Google Scholar]
  10. Iacopetta, Domenico Chitosan-based Schiff bases (CSBs) and their metal complexes: Promising antimicrobial agents. Molecules 2025 30 2 207 10.3390/molecules30020207 39860077
    [Google Scholar]
  11. Nicolaou K.C. Advancing the drug discovery and development process. Angew. Chem. Int. Ed. 2014 53 35 9128 9140 10.1002/anie.201404761 25045053
    [Google Scholar]
  12. Agamah F.E. Mazandu G.K. Hassan R. Bope C.D. Thomford N.E. Ghansah A. Chimusa E.R. Computational/in silico methods in drug target and lead prediction. Brief. Bioinform. 2020 21 5 1663 1675 10.1093/bib/bbz103 31711157
    [Google Scholar]
  13. Ok, Emmanuel A comprehensive review of the diverse applications of novel schiff bases and their metal complexes 2025
    [Google Scholar]
  14. Zhang J. Xu L. Wong W.Y. Energy materials based on metal Schiff base complexes. Coord. Chem. Rev. 2018 355 180 198 10.1016/j.ccr.2017.08.007
    [Google Scholar]
  15. Stockwell J. Abdi N. Lu X. Maheshwari O. Taghibiglou C. Novel central nervous system drug delivery systems. Chem. Biol. Drug Des. 2014 83 5 507 520 10.1111/cbdd.12268 24325540
    [Google Scholar]
  16. Asif, Mohammad Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives. Int. J. Med. Chem. 2014 395637 10.1155/2014/395637 25692041
    [Google Scholar]
  17. Jafari E. Quinazolinone and quinazoline derivatives: Recent structures with potent antimicrobial and cytotoxic activities. Res. Pharm. Sci. 2016 11 1 1 14 27051427
    [Google Scholar]
  18. Wang D. Gao F. Quinazoline derivatives: Synthesis and bioactivities. Chem. Cent. J. 2013 7 1 95 10.1186/1752‑153X‑7‑95 23731671
    [Google Scholar]
  19. Chauhan V.I.S.H.E.S.H. Hauhan V. A review: The biological activities of schiff bases. App Org Chem. 2023 7 5 97 109 10.55041/IJSREM21313
    [Google Scholar]
  20. Kumar S. Kumar A. Synthesis, computational and pharmacological evaluation of 7-(2-(2- (3- (Substituted Phenyl) Acryloyl) Phenoxy) Ethoxy)-4-Methyl-2H-Chromen- 2-Ones as CNS agents. Cent. Nerv. Syst. Agents Med. Chem. 2023 23 1 57 64 10.2174/1871524923666230130134501 36717998
    [Google Scholar]
/content/journals/cnsamc/10.2174/0118715249355436250806100850
Loading
/content/journals/cnsamc/10.2174/0118715249355436250806100850
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.


  • Article Type:
    Research Article
Keywords: receptor ; Chromatography ; skeletal muscle ; antianxiety
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test