Celecoxib Derivatives Containing Pyrazole Linked‐Sulfonamide Moiety: Carbonic Anhydrase I–II and Acetylcholinesterase Inhibition Profiles, Molecular Docking Studies

Abstract

AbstractHeterocyclic pyrazole compounds have cytotoxic, anticancer, antimicrobial, anti‐inflammatory properties, as well as their derivatives containing sulfonamide moiety, show superior effects on inhibiting various enzymes. Pre‐synthesized celecoxib‐derived compounds were studied for their inhibitory effects on human carbonic anhydrase (hCA I and hCA II) isoforms and acetylcholinesterase (AChE). The compound containing 2,3 dimethoxyphenyl functional groups from the celecoxib derivative containing this sulfonamide moiety showed a strong inhibitory effect with Ki values at 21.70±2.50 nM, 4.70±2.20 nM, and 4.58±0.80 nM for hCA I, hCA II, and AChE, respectively. In addition, these compounds were evaluated against acetazolamide (AZA) and tacrine (TAC), which are used as standard inhibitors for the studied enzymes. The compound obtained as a result of the reaction of pyrazole compounds with propionic anhydride and showing the best inhibition effect had higher inhibitory activity than the standard inhibitors we used. In addition, molecular docking analyses to the strongest inhibitor were performed to identify possible binding mechanisms with the active sites of all three enzymes. Based on both in vitro and molecular docking analysis results, this compound was determined as a potential inhibitor of AChE, hCA I, and hCA II isoenzymes.