Alzheimer hastalığının tedavisine yönelik yeni hidrazon türevlerinin sentezi ve biyolojik aktivitilerinin değerlendirilmesi

In recent years, Alzheimer's disease has been addressed as a silent epidemic neurodegenerative disorder. Due to its complex pathophysiology, there is significant scientific interest in developing effective treatments that go beyond symptomatic relief. The goal is to raise the patient's quality of living and reduce the mortality rate associated with Alzheimer's, a goal that has not yet been fully realized, thus keeping Alzheimer's research in focus. In this PhD thesis, we designed a set consisting of 27 hybrid molecules based on the molecular structure of donepezil, as an acetylcholinesterase inhibitor (AChEI). The hybrid molecules feature dihydrothiazolyl hydrazone and phenyl piperidine moieties. The produced compounds were assessed for their biological activity and cytotoxicity using IR, NMR, and HRMS spectroscopy. The biological activity studies comprise that the compound coded D1.f was the most active one among the other 27 derivatives against AChE enzyme. The inhibitory activities (IC50 values) of this compound on the relevant enzymes range from 0.039 ±0.001 μM, and its IC50 values in the NIH3T3 fibroblast cell line value as 3.324±0.155 μΜ with the highest value of selectivity index SI 85.231 among other derivatives. Among all derivatives, D1.f demonstrated the best AChEI activity and optimal docking poses and stability in the molecular dynamics studies. based on the obtained data, molecule D1.f was a candidate for further investigations. Keywords: Acetylcholine Esterase Inhibitors, cytotoxicity, Alzheimer's Disease, Piperidine, thiazole ring, Hantzsch method