Exploring Anti-inflammatory Potential of Thiazolidinone Derivatives of Benzenesulfonamide via Synthesis, Molecular Docking and Biological Evaluation.

Abstract

The present study reports the synthesis and biological evaluation of thiazolidinone derivatives bearing benzenesulfonamide investigated for cyclooxygenase-2 (COX-2) inhibitory activity and in vivo anti-inflammatory activity. The synthesis of 4-(4-oxo-2-substituted-1,3-thiazolidin-3-yl) benzenesulfonamide derivatives were carried out by conventional synthesis, involves the one-pot condensation reaction of sulfanilamide. The synthesized compounds were evaluated against COX-1 and human recombinant COX-2 by using colorimetric enzyme assay kit and in-vivo study was carried out by carageenan induced rat paw edema method. Five derivatives 3a, 3b, 3f, 3g, and 3j showed pronounced COX-2 percentage inhibition (55.76, 61.75, 46.54, 43.32, and 49.77% respectively). Structure activity relationship suggested that the compound with a 4-hydroxy group on phenyl ring leads to more selective inhibition of COX-2 than celecoxib, which is supported by molecular docking study. In silico ADME properties showed that compound 3a, 3b, 3f, 3g, and 3j complies Lipinski's rule of five and show no violation. Molecular docking study divulged the binding interactions of thiazolidinone derivatives into the active site of COX-2 and thereby helps to design the potent inhibitors. The overall studies inferred that compound 3b rendered it as a good leadcandidate for the further development of more potent anti-inflammatory agent.