Design of new inhibitors against Alzheimer's disease using molecular modeling and evaluation of the drug similarity and admet profiles of these inhibitors using different in silico methods

Alzheimer's disease is a multifactorial disease characterized by amyloid beta deposition, hyperphosphorylation and decreased cholinergic transmission. From this point of view, in this study, the inhibitory effects of cinnnamaldehyde and vanillin Schiff bases and amine derivatives on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), beta secretase (BACE1), glycogensynthase kinase 3 beta (GSK3ß), histondeacetylase 2 and 6 enzymes were evaluated. First of all, by using the "Swiss Target Prediction and Similarity Ensembl Approach" tools, which enzymes were determined by the active substances, molecular docking and drug similarity-toxicology analyzes were performed with the "Autodock 4.2.2" software. As a result of the analysis, it was observed that all compounds had inhibitory effects on at least two target enzymes. In addition, it was determined that all compounds comply with Lipinski's 5 rule and are within toxicological limits. As a result, it is thought that the compounds can be evaluated in a multi-drug strategy and used as a neuroprotective anti-Alzheimer's agent.