Abstract:

Alzheimer's disease is one of the most common neurodegenerative diseases in the world. The increasing number of patients with the aging of the world population and the absence of a radical treatment create a need for the development of new compounds. Cholinesterase inhibitors are frequently used against the disease. The two known cholinesterase’s are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In AD-affected brains, the amount of AChE, the main enzyme responsible for ACh hydrolysis, is reduced under normal conditions, while the concentration of BChE is maintained or even increased.The 6-(2-(4-substitutedpiperazin-1-yl) acetyl)-2H-benzo[b][1,4] oxazin-3(4H)-one (1a-1h) series consisting of 8 new compounds was synthesized. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and HRMS spectroscopy data. The in vitro cholinesterase (ChE) inhibitory activity of the compounds was evaluated using the Ellman's method. Among the synthesized compounds, the compounds 1b and 1e showed significant inhibitory activity against acetylcholinesterase (AChE). When the acetylcholinesterase inhibitory potentials of the synthesized compounds are examined, it is seen that promising results have been achieved. Additionally, in silico molecular docking studies with active derivatives show that active compounds have settled in the enzyme active site and interact with amino acids in this region. It is planned to reach more effective new compounds with the modifications made on the obtained compounds.

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