In Silico and In Vitro Analysis of Acetylcholinesteraseand Glutathione S-Transferase Enzymes of Substituted Pyrazoles

Abstract— A series of substitute pyrazole compounds including azide, acetyl, triazole, morpholine, piperidine, and pyrrolidine moieties were synthesized and their structures were elucidated by NMR, HPLC and mass spectroscopy. The inhibition efficiencies of all novel compounds against acetylcholinesterase (AChE) and glutathione S-transferase (GST) enzymes were investigated. In vitro studies revealed that the inhibitory activities of substitute pyrazole compounds were determined with K_i values in the range of 0.11–0.49 µM for AChE, and 0.12–0.91 µM for GST, respectively. Furthermore, the molecular docking studies of the detailed interactions between the pyrazole compounds and AChE-GST enzymes were identified with bonding type, distance, hydrophobic bonds and hydrogen bonds. The binding energies of the AChE-pyrazole analogs’ complexes were found between –5.5 and –9.3 kcal/mol, and the binding energies of the GST-pyrazole analogs’ complexes were found between –5.9 and –9.2 kcal/mol.