Potansiyel AntiAlzheimer Etkili Takrin Türevleri Üzerine Çalışmalar
Project no. 23635 · Status: Kapanmış · 2022
Summary
<p>Alzheimer's disease is a progressive neurodegenerative disease. The risk of Alzheimer's</p><p>disease, which is the most common cause of dementia, increases with aging. This situation</p><p>creates a significant health cost in countries with an increasing death age.</p><p>Alzheimer's disease is associated with decreased acetylcholine levels, intracellular</p><p>neurofibrillary tangles, extracellular amyloid b plaque formation, and hyperphosphorylation of</p><p>tau protein.</p><p>The classical roles of the AChE enzyme are performed through the CAS. AChE enzyme has</p><p>also been discovered to have a nonclassical role in mediating amyloid b plaque deposition</p><p>through PAS. After the discovery of this situation, dual binding site inhibitors began to be</p><p>developed.</p><p>Since the "Single Molecule - Single Target" strategy was insufficient in diseases with</p><p>multifactorial pathology such as Alzheimer's, "Multi-Target Directed Ligands" (MTDL) came</p><p>into focus. MTDLs are formed by combining two different molecules interacting with different</p><p>target sites, while preserving their effect at both target sites.</p><p>Within the scope of this project, tacrine hybrid bearing hydrazone functional group was</p><p>designed. The designed compound was synthesized in 3 steps. In the first step, 9-chloro-1,2,3,4-</p><p>tetrahydroacridine compound was obtained. In the second step, 9-hydrazino-1,2,3,4-</p><p>tetrahydroacridine hydrochloride structure was synthsized. In the third step, we obtained 9-(2-</p><p>[2 methoxyphenyl]methylidene)-hydrazinyl-1,2,3,4-tetrahydroacridine by substituting the 9-</p><p>hydrazino-1,2,3,4 tetrahydroacridine compound with 2-methoxybenzaldehyde.</p><p>The synthesized final compound was purified and its structure elucidated by 1HNMR, IR and</p><p>mass spectroscopic methods. The bioactivity of the final compound was measured and</p><p>compared with the reference compound tacrine, and the results were discussed.</p><p>The final compound synthesized within the scope of this project was reported for the first time</p><p>in this study.</p>