Lactoperoxidase Inhibition of Celecoxib Derivatives Containing the Pyrazole Linked‐Sulfonamide Moiety: Antioxidant Capacity, Antimicrobial Activity, and Molecular Docking Studies

ABSTRACT Celecoxib derivatives that contain the pyrazole‐linked sulfonamide moiety were synthesized, and the in vitro inhibitory impacts of the aforesaid compounds against the lactoperoxidase (LPO) enzyme were researched. To this end, LPO was purified using the affinity chromatography technique with a yield of 12.63% (319.23‐fold). The results showed that the aromatic pyrazole compound (compound 1) containing 2,3‐dimethoxyphenyl functional groups was the most effective LPO inhibitor with a Ki value of 3.2 ± 0.7 nM and noncompetitive inhibition type. The second section of the study tested the previously synthesized compounds to reveal their antioxidant and antimicrobial properties. The above‐mentioned compound also displayed high activity levels compared to standard antibiotics and antifungals, while all other compounds also showed antibacterial activity. In the three antioxidant methods we used, the compound with 2,5‐dimethoxy phenyl groups obtained from the reaction of the aromatic pyrazole compound with propionic anhydride in the presence of NEt3 displayed the highest activity. Furthermore, molecular docking and molecular mechanics studies were conducted to complement and validate the experimental findings. The results obtained from these computational analyses are highly consistent with the experimental data. The inhibitory effects of celecoxib‐derived compounds containing pre‐synthesized pyrazole‐linked sulfonamide moiety on the lactoperoxidase enzyme, which we obtained from bovine milk in high yield and purity with a fast and effective one‐step affinity technique, were investigated. These compounds were also tested to reveal their antioxidant and antimicrobial properties. Molecular docking and molecular mechanics studies were also performed to complement and validate the experimental findings. The results obtained from these computational analyses show a high level of consistency with experimental data.