Yeni 1,3,4-oksadiazol türevleri ve biyolojik aktivitelerinin araştırılması

1,3,4-Oxadiazole is a heterocyclic scaffold that is functionalized widely in both industrial and pharmaceutical disciplines. Recently, a large number of 1,3,4-oxadiazole-containing structures have been used to treat diverse types of diseases. Alzheimer's disease (AD) is a complex, multifactorial and progressive disease characterized by the death of cholinergic neurons and upregulation of monoamine oxidase (MAO-B) enzyme. In this thesis, a series of novel 1,3,4-oxadiazole-quinoline hybrids have been synthesized and biologically evaluated as potential inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase and MAOs enzymes. The chemical structures of all final structures were confirmed using IR, 1H-NMR, 13C-NMR and mass spectrometry. Among all the compounds, 5a, 5c and 6a possessed substantial activity against AChE with IC50 values of 0.033 µM, 0.096 µM and 0.177 µM, respectively. The binding modes and structural activity relationship (SAR) of the most potent structures 5a, 5c and 6a have been provided and confirmed using molecular docking. Compound 5a has established unique binding properties by interacting with both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the AChE providing an additional neuroprotective effect. The physicochemical properties of the synthesized structures have been also evaluated