This article and associated images are based on a poster originally authored by Nermeen Ali, Heather Coleman, Azza Taher, Marwa Sarg and Noha Hilmy Elnagdi and presented at ELRIG Drug Discovery 2025 in affiliation with Ulster University, Cairo University, October 6 University, Al-Azhar University and Modern University for Technology and Information.
This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.
Introduction
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain and inflammation by inhibiting the cyclooxygenase (COX-1 and COX-2) enzymes involved in prostaglandin synthesis 1.
However, NSAIDs can have many adverse effects, including gastrointestinal bleeding 2. Some examples of pyrazole derivatives, such as Deracoxib, Ramifenazone, and Pyraclonil, have been reported as potent NSAIDs.3
Objective
To rationally design, synthesize, and biologically evaluate a new series of pyrazole-pyrazoline derivatives as structural analogues of Celecoxib, Indomethacin, and Floctafenine. The aim is to develop selective COX-2 inhibitors possessing enhanced antiinflammatory and analgesic efficacy and improved safety profiles.
Method
Novel pyrazole-pyrazoline derivatives were synthesized via the Vilsmeier–Haack reaction followed by condensation and cyclization steps to yield amide and ester analogues. Structures were confirmed using elemental analysis, IR, ¹H NMR, and MS spectroscopy.
Anti-inflammatory activity was assessed by the carrageenan-induced paw oedema test, while analgesic activity was evaluated with the acetic acid-induced writhing test in rats. Molecular docking was performed on the COX-2 enzyme (PDB ID: 4Z0L) to evaluate binding interactions and rationalize biological results.
Results
Most of the newly synthesized derivatives showed significant anti-inflammatory and analgesic activities compared with Indomethacin. Compounds 14b, 15b, and 22 produced the highest oedema inhibition (28.6-30.9 %) and analgesic effects (up to 84.5 % inhibition).
Docking studies revealed that compound 14b exhibited the strongest COX-2 binding affinity (-16.39 kcal/mol), forming key H-bonds with Arg120, Val349, and Ala527. The correlation between docking scores and in vivo activity supports their potential as selective COX-2 inhibitors
Graphs
Preparation of the pyrazole carboxylic acids 9a-f. Image Credit: Image courtesy of Nermeen Ali et al., in partnership with ELRIG (UK) Ltd.
Preparation of pyrazole amides 13a,b, 14a,b and pyrazole esters 15a,b. Image Credit: Image courtesy of Nermeen Ali et al., in partnership with ELRIG (UK) Ltd.
Preparation of the pyrazole chalcones 17a,b, and bipyrazoles 18a,b. Image Credit: Image courtesy of Nermeen Ali et al., in partnership with ELRIG (UK) Ltd.
Preparation of Floctafenine chalcone 21 and pyrazoline 22. Image Credit: Image courtesy of Nermeen Ali et al., in partnership with ELRIG (UK) Ltd.
Docking of 14b into COX-2 (4Z0L). Image Credit: Image courtesy of Nermeen Ali et al., in partnership with ELRIG (UK) Ltd.
Conclusion
Structure-activity relationship (SAR) evaluation demonstrated that extending the alkyl chain and incorporating amide or ester functionalities significantly enhanced the anti-inflammatory and analgesic profiles.
Compounds 13b, 14b, and 15b with longer carbon chains exhibited superior anti-inflammatory activity (28.6-30.9 % inhibition), whereas pyrazoline analogues 18 and 22 showed the highest analgesic response (up to 84.5 % inhibition).
Cyclization to pyrazolines and fusion with a quinoline scaffold improved both potency and COX-2 selectivity. Molecular docking corroborated the experimental findings, identifying compound 14b as the most active through key interactions with Arg120, Arg513, Ser119, Val349, and Ala527 within the COX-2 active site.
References
- Agrawal, N. (2025). A Comprehensive Review on the Advancements of Dual COX‐2/5‐LOX Inhibitors as Anti‐Inflammatory Drugs. Chemical Biology & Drug Design, 105(5), pp.e70114–e70114. DOI: 10.1111/cbdd.70114. https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70114
- Joshi, G.P., Henrik Kehlet and Lobo, D.N. (2024). Nonsteroidal anti-inflammatory drugs in the perioperative period: current controversies and concerns. British Journal of Anaesthesia. DOI: 10.1016/j.bja.2024.10.018. https://www.sciencedirect.com/science/article/abs/pii/S0007091224006524.
- Ghoneim, M.M., et al. (2024). Review of the recent advances of pyrazole derivatives as selective COX-2 inhibitors for treating inflammation. Molecular Diversity. DOI: 10.1007/s11030-024-10906-9. https://link.springer.com/article/10.1007/s11030-024-10906-9.
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Last Updated: Nov 26, 2025