bioactive sulfonyl hydrazones with indole scaffold, characterization, adme properties, molecular docking studies and investigation of inhibition on choline esterase enzymes for the diagnosis of Alzheimer’s disease

Abstract Background Alzheimer’s disease (AD) is a progressive and neurodegenerative disease that is primarily seen in the elderly population and is clinically characterized by memory and cognitive impairment. This study aimed to find new ChE inhibitors. Method The structures of the synthesized compounds were characterized by 1 H NMR, 13 C NMR and HRMS. The effects of the synthesized hydrazones on acetylcholinesterase and butyrylcholinesterase enzymes were measured using the microplate assay described in the Ellman test, with modifications added by López (2002). Result According to the results, all the synthesized compounds inhibited AChE and BChE enzymes. When the IC 50 values were compared, the compounds with indole scaffold and donepezil fragment showed potent inhibitory activity on the AChE enzyme. In addition, the predictive properties of all compounds in terms of drug similarity were scanned using five Lipinski rules and ADME. Also, to evaluate the binding interactions between the hydrazone compounds and enzymes, molecular docking studies were performed and the compounds with the best inhibition effect were tested. Promisingly, the compound 3d showed good permeability in the PAMPA‐BBB model and high in vitro antioxidant activity. Conclusion Both in vitro and in silico results showed that two compounds could act as promising inhibitors of AChE and the data provided the way to guide future studies. Funding This research was funded by the Bulgarian National Science Fund (Grant KP‐06‐Н63/11 14.12.2022).