Molecular Insights into Benzene Sulphonamides Substituted Diarylpyrazoles As Cyclooxygenase-2 Inhibitor and Its Structural Modifications

The use of NSAIDs increases from year to year because of the increasing age of the population. Hence a safer, economical and more potent novel cox-2 inhibitors with minimal side effects and high safety margins were to be developed. For this, a series of 44 diaryl pyrazole benzene sulphonamide derivatives with their cyclooxygenase-2 inhibitory activity were subjected to QSAR studies to derive a correlation between biological activity and physicochemical properties using QSARINS software. The best two-descriptor QSAR model was developed which showed better results of correlation coefficient R2 = 0.6530, CCC tr = 0.7901, CCCcv = 0.7262, R2ext = 0.8225, and CCCext = 0.8930. The two descriptors obtained were 3D-MoRSEC-6 and GATSe3, which explains that the atomic charges and spatial autocorrelation play a key role in COX-2 inhibitory activity. New lead molecules were designed based on key structural findings followed by in silico-screening study. These newer molecules were predicted for their COX-2 inhibitory activity using the obtained two-descriptor model. The designed molecules were docked using Autodock v 4.2.6 with PDB id 5F19 and were also predicted for ADMET properties. Both the hydrophilic as well as hydrophobic parts of the residues of active site regions interacted with best predicted active compounds. The study suggests crucial properties and key interactions that are essential for potent enzyme inhibition and find this series as promising leads for further development as novel cyclooxygenase agents.