OBJECTIVES: Celecoxib is a nonsteroidal anti-inflammatory drug inhibiting enzyme cyclooxygenase-2 (COX-2). The drug was introduced in 1990s. In the work presented here, affinity of celecoxib to enzyme acetylcholinesterase (AChE) is inferred. METHODS: Inhibition of human AChE by celecoxib was tested using standard spectrophotometric Ellman´s method and extrapolation of experimental data by Dixon plot. Interaction between AChE and celecoxib was also predicted by molecular docking using Swiss dock software. RESULTS: A non-competitive mechanism of inhibition was revealed and equilibrium inhibitory constant equal to 313±40 µmol/l was determined. Comparing to AChE, celecoxib was not proved as an inhibitor of enzyme butyrylcholinesterase (BChE). The lowest ΔG was equal to -7.78 kcal/mol. In this case, celecoxib stacked sulfonamide moiety between TYR 337 and TYR 341 of alfa anionic subsite of active site. Cation-Π interactions appears to be responsible for the inhibition. CONCLUSIONS: Though the here revealed and characterized inhibition has lower effect in real conditions than inhibition of COX-2, the inhibitory effect would be utilized in the next research and development of new AChE inhibitors.

Department of Geology and Pedology Mendel University in Brno Brno Czech Republic

Faculty of Military Health Sciences University of Defence Hradec Kralove Czech Republic