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VOL. 10, ISSUE 4 (2026)
Molecular modeling, synthesis and biological evaluation of novel pyrazole derivatives as potential anti-inflammatory agents
Authors
Suresh Govind Pagare1, Dr. Neelu Jain
Abstract
Inflammation-related diseases continue to be amongst the most important
causes of morbidity worldwide and the nonsteroidal anti-inflammatory drugs
(NSAIDs) currently in clinical use are often hampered by gastrointestinal and
cardiovascular toxicity (Ahmadi et al., 2022) [2]. Pyrazole
is a 5-membered N, N-heterocycle that serves as the core structure of numerous
anti-inflammatory drugs with N, N-heterocycle cores such as celecoxib, which is
a common and effective treatment for gastrointestinal tract inflammation, and
is a popular structure for medicinal chemists because of its synthetic
flexibility and favorable pharmacokinetic profile (Ebenezer et al.,
2022; Turones et al., 2021) [8, 18]. A series of twelve new
1,3,5-triarylpyrazole derivatives (4a-4l) have been designed, prepared and
investigated as anti-inflammatory agents, two of which (4k and 4l) contain the
trifluoromethyl and sulfamoyl (SO2NH2) groups present in the clinically used
COX-2 inhibitor celecoxib. The target compounds were synthesized by two step
reaction sequence where the first reaction involves Claisen-Schmidt
condensation of substituted acetophenones with aromatic aldehyde to get
chalcone intermediate and second step is followed by its consecutive
cyclo-condensation with phenyl hydrazine and oxidative aromatization reaction
(Goyal et al., 2021) [11]. Melting point determination,
Fourier-transform infrared (FT-IR), proton and carbon nuclear magnetic
resonance (1H NMR, 13C NMR) and mass spectral analysis were used for the
characterization of all the synthesized compounds. The in-silico analysis was
performed using AutoDock Vina 1.2.0 software and a molecular docking study of
the observed structure–activity relationship using AutoDock Vina 1.2.0 software
was performed against the cyclooxygenase-2 (COX-2) active site (PDB: 3LN1). The
anti-inflammatory activity was assessed by in vitro COX-2 inhibition
assay and in vivo carrageenan-induced rat paw oedema model and compared
with the activity of diclofenac sodium and celecoxib. The sulfamoylphenyl
pharmacophore containing compound 4l was the most active compound in the series
with a COX-2 IC50 of 0.14 μM, selectivity index of 22.9 and 72.1% oedema
inhibition after 4 h, which is higher than both of the reference standards, and
4k (trifluoromethyl) and 4f (dichloro) also exhibited strong and selective
activity. The docking poses of 4l displayed favourable hydrogen-bonding and
hydrophobic contacts in the secondary pocket of COX-2, which is similar to the
binding mode of celecoxib. Overall, these studies offer support for the
development of pyrazole scaffold and specifically for sulfonamide derivative as
a model for designing safer and more selective anti-inflammatory agents.
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Pages:7-14
How to cite this article:
Suresh Govind Pagare1, Dr. Neelu Jain "Molecular modeling, synthesis and biological evaluation of novel pyrazole derivatives as potential anti-inflammatory agents". International Journal of Chemistry Studies, Vol 10, Issue 4, 2026, Pages 7-14
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