Synthesis and biological evaluation of new cholinesterase inhibitors

Alzheimer's disease (AD) is a neurodegenerative disorder mostly influencing the elderly and causes death due to dementia. The main pathogenic feature connected with the progression of this multifactorial disease is the weakening of the cholinergic system in the brain. Cholinesterase (ChEs) inhibitors are recognized as one of the most promising targets in the treatment of AD. The inhibition of both enzymes has been approved as an appropriate therapeutic strategy to reduce the symptoms of disease and prevent disease progression; as well. The speed of medication explore has quickened detectably during the recent decade. Despite efforts to discover the original drugs, a radical treatment for this disease has not been found yet. A few drugs are approved by Food and Drug Administration to treat symptoms of AD. These medications are not ready to change or anticipate malady progression, they are, rather, palliative in easing the symptoms of malady. Inspired by what previously mentioned and by using simple and efficient synthetic way, 2-(9-acridinylamino)-2-oxoethyl piperazine/piperidine/morpholinecarbodithioate derivatives incorporating 9-aminoacridine and Donepezil like analogues were synthesized for the targeted modulation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. In general, we have achieved our desired aim, thus, eight derivatives demonstrated a specific and promising action against BChE. Furthermore, compound 4n showed probable inhibitory activity against both enzymes. It has been found that the active compounds are well tolerated in the cytotoxicity test. Possible interactions between the lead compound 4n and BChE enzyme were determined by a docking study. The findings obtained within this thesis will contribute to the development of new and effective synthetic anti-Alzheimer compounds and will ideally encourage future screening against AD.