Background: Cyclooxygenase (COX-2) inhibitors have been developed to provide better
anti-inflammatory and analgesic efficacy than those of traditional NSAIDs. Several compounds
having selective COX-2 inhibitors such as SC-558, Celecoxib, Rofecoxib, Valdecoxib and Etoricoxib
are marketed as new generation NSAIDs and block the production of prostaglandins (PGs)
in inflammatory cells. New anti-inflammatory agents with improved potency and safety profile are
Objective: As a part of our continuation research work towards new anti-inflammatory agents, the
synthesis of N-substituted aryl/heteroaryl-pyrazole-1yl benzene sulfonamide (Celecoxib) derivatives,
their anti-inflammatory activity in both methods in vitro and in vivo and molecular docking
study on COX-2 enzyme will be discussed in this study.
Methods: A series of N-substituted (aryl/heteroarylpyrazol-1-yl)benzenesulfonamide (Celecoxib)
derivatives was synthesized and characterized them using IR, NMR (1H and 13C), mass and elemental
analyses. Anti-inflammatory activity of the title compounds was evaluated by in vitro initially
using albumin denaturation and membrane stabilization methods, enzymatic activity against
COX-2 enzyme using colorimetric assay and then in vivo by carrageenan induced paw oedema
and cotton pellet induced granuloma methods. The docking study was performed, to find the binding
mode of the title compounds with the binding site of the COX-2 enzyme.
Results: The biological activity screening data disclosed that some of the compounds 5b, 5e, 5f
and 5i exhibited potent anti-inflammatory activity in both methods, in vitro and in vivo. The enzymatic
assay on COX-2 enzyme demonstrated that few compounds potently inhibit COX-2 enzyme
activity with IC50 of <0.89 μM. Unexpectedly, compound 5e (IC50, 0.62±0.17 μM) showed
more potent COX-2 inhibited activity than that of parent drug, celecoxib (IC50, 0.62±0.25 μM) and
the standard, flufenamic acid (IC50, 0.71±0.12 μM).
Conclusion: The bio-screening data, in vitro and in vivo anti-inflammatory activity and COX-2
enzymatic assay revealed that few N-substituteed aryl/heteroaryl-pyrazol-1-yl) benzene sulfonamides
showed potent activity and compound 5e showed more potent COX-2 inhibit activity than
that of parent drug, celecoxib and the standard, flufenamic acid. Moreover, all the newly synthesized
title products were bonded well with good binding energies in the sight of COX-2 enzyme.
Therefore, the described study might provide sustained information to the development of new series
of derivatives with potent drug like activity.