Synthesis of new thiosemicarbazone derivatives and investigation of dual AChE and MAO-B inhibitory effects

Alzheimer's disease is a progressive and fatal chronic disease characterized by behavioral symptoms and loss of cognitive and physical function. It is the most common cause of dementia. Hyperphosphorylation of tau proteins, β amyloid protein aggregation, reduction of neurotransmitters and oxidative stress mechanisms are predicted as neuropathological findings of Alzheimer's disease and AChE inhibitors are used in the symptomatic treatment. In this study; 15 thiosemicarbazone derivative compounds were synthesized. Analysis of the obtained compounds; 1H-NMR, 13C-NMR and Mass spectroscopic methods are illuminated by the analysis findings. The inhibition effect of the obtained compounds on cholinesterase and monoaminoxidase (MAO) enzymes was investigated. None of the synthesized compounds showed significant activity on butyrylcholinesterase (BChE) enzyme. 3b, 3c, 3e, 3k, 3l, 3m, 3n and 3o coded compounds; Acethylcholinesterase (AChE) and 3f, 3i, 3k, 3l, 3m, 3n, 3o coded compounds also showed remarkable effects on MAO-B enzymes. Within the scope of the thesis, the structure of AChE and MAO-B enzyme active sites has been clarified by molecular modeling studies. For the selected compounds, docking studies were performed and the enzyme active site and binding points were determined. It was revealed that the strongest interaction with AChE and MAO-B enzyme active sites was observed with the 3k coded compound.