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

Alzheimer's disease (AD) is a multifactorial neurological disorder that is the most common form of dementia among the elderly. While various pathogenic processes have been proposed to explain the pathophysiology of Alzheimer's disease, the exact cause remains a mystery to scientists. Because of the disease's complex pathological process, current conventional treatments including mono-targeted therapies and combination therapies are considered insufficient to cure or slow the progression of the disease. As a result, researchers are increasingly concentrating on the development of novel multi-targeted drugs (MTDs) that can act on several targets at the same time. In this thesis, the characteristic features of the 1,3,4-thiadiazole heterocyclic ring and the tricyclic hydrocarbon adamantane were used to design and synthesize novel derivatives. The chemical structures of all synthesized compounds were elucidated by using IR, 1H-NMR, 13C-NMR, and High-resolution mass spectrometry (HR-MS). These derivatives were investigated for their in vitro activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidases (MAO-A and MAO-B) which have been linked to pathogenic pathways in AD. According to the activity results, compounds 3a, 3b, 3d, 4a and 4b showed remarkable inhibition activity against AChE. Compounds 3a, 4a and 4b showed inhibition activity against MAO-B while none of the compounds showed inhibition activity against BChE and MAO-A. Among these active compounds, 3a, 4a and 4b showed dual inhibition activity, however compound 4a was the most promising dual inhibitor candidate. Additionally, Molecular docking studies for the most active compounds were performed on both AChE and hMAO-B crystal structures to investigate the binding interactions with the enzyme's active site.