Synthesis, BuChE and AChE Enzyme Inhibition and Molecular Docking Studies of Hydrazide-Hydrazone Schiff Base Compound Containing Propargyl/Pyridine Moiety

The focus of this study was the preparation and structural characterisation of hydrazine hydrazone Schiff base compounds containing a propargyl group in a new structure, using common spectroscopic and analytical methods. Since Hydrazide-hydrazone compounds are known to possess high biological activity, it was thought that compound 2a synthesized by us could be an important inhibitor for the treatment of Alzheimer's disease. A screening was performed on the Hydrazide-hydrazone Schiff base compound (2a) to determine its potential as an inhibitor of cholinesterase. The enzyme inhibition values of compound 2a were determined as IC50= 42.72±0.01 and IC50= 39.19±0.04 µM for AChE and BuChE, respectively. Compared to the standard compound Galantamine (IC50= 32.45±0.06 and IC50= 40.25±0.03 µM), it exhibited low activity for AChE. It exhibited a higher activity for BuChE. When compared to the standard drug galantamine, the compound showed only moderate inhibitory activity. Ki values of 1.25 and 2.32 μM were determined as the substance exhibited milder activity against AChE and BuChE, respectively. Molecular docking studies also revealed that these hydrophilic and hydrophobic interactions are instrumental in conferring the compound's strong binding affinity. They also revealed that these interactions are instrumental in the compound's potent inhibitory activity. These results indicate that compound 2a exhibits activity against both enzymes.