Bazı yeni sübstitüe benzofuran türevlerinin sentezleri ve biyolojik aktivite çalışmaları

Benzofuran is a fused bicyclic scaffold that is functionalized widely in the industrial and pharmaceutical sectors. The economic benefits and ease of synthesizing benzofuran make it a target for further research studies. In this thesis, benzofuran was selected as a scaffold to design new therapeutic agents. After reviewing the literature, benzofuran scaffold was found suitable for the design of new acetylcholine esterase (AChE) inhibitors that can be employed in the palliative treatment of Alzheimer's disease (AD). A total of 42 hybrid benzofuran and piperazine derivatives were designed. The designed molecules were planned to have binding fit in the active site of the enzyme similar to that of the reference AChE inhibitor donepezil. All of the target products were synthesized and analyzed by 1H NMR, 13C NMR, IR, and mass spectrometry. The biological activity studies were achieved using in vitro assay on AChE, butyrylcholine esterase (BChE) and β-amyloid. The results showed that four compounds namely D25, D30, D40, and D41 were active and inhibited AChE while no activity was observed against BChE. On the other hand, compounds D25 and D41 showed good Aβ aggregation inhibitory activity comparable to the reference inhibitor, while compounds D30 and D40 displayed a weaker Aβ aggregation inhibitory activity. The cytotoxicity investigation of the active compounds showed that these compounds have plausible safety. Molecular docking study was achieved to analyze the binding modes of the active compounds. The four compounds D25, D30, D40, and D41 are thought to be useful agents in the treatment strategies of AD and accordingly are recommended for further studies.