تاريخ مجلس الدراسات العليا

2024-02-11

اسم الطالب

حنين بهجت الربيعي

ملخص الرسالة

Alzheimer's disease (AD) ranks among the primary contributors to mortality among elderly population on a global scale. Some commonly observed indicators of AD encompass memory loss, confusion and disorientation, difficulties with problem-solving and planning, the primary cause of this condition is the damage to cholinergic neurons in the forebrain and hippo-campus; resulting in reduction in the level of acetylcholine (ACh), another significant factor contributing to this condition is the activation of reactive oxygen species, which includes oxidative stress in various regions of the brain. Currently, the available treatment options for this neurodegenerative condition primarily focus on managing the associated symptoms rather than addressing the underlying cause. Tacrine was the first acetylcholinesterase inhibitor (AChEI) introduced into clinical use for management of AD, which was approved for use in the United States in 1993. Due to ongoing concerns regarding the safety and availability of alternatives acetylcholinesterase inhibitors (AChEIs), Tacrine was withdrawn from USA market in 2013. In this study, a novel hybrid Tacrine derivative was synthesized, which exhibits dual biological action aimed at slowing down the progression of AD, which was monitored through using TLC, GC-MS, 1H-NMR and 13C-NMR, then conjugated with Chitosan nanocomposite which was monitored using TGA and XRD. The in vitro evaluation of compound 2 was conducted to assess its anti-cholinesterase activity using the Ellman's assay. The results obtained from the study demonstrated that compound 2 exhibited significant concentration-dependent inhibition activity of AChE enzyme with (IC50 = 0.735 ?M ± 0.041 , p<0.05) compared to standard drug Tacrine (IC50 0.00153 ?M ± 0.00015, p<0.05). The utilization of nanocomposites as drug carries is of great importance due to several factors. These include their high carrier capacity, high solubility, ability to incorporate both lipophilic and lipophobic drugs, as well as the potential for various administration routes. The incorporation of compound 2 with chitosan nanoparticles to form compound 2-CSNPs nanocomposites was prepared through ionic gelation method. The release profile of compound 2 from compound 2-CSNPs nanocomposites was studied at pH 7.4, with sustained release of the compound 2 from nanocomposites for up to 1400 minutes. Key words: Alzheimer's disease, dementia, acetylcholine, acetylcholine esterase enzyme, oxidative stress, reactive oxygen species, antioxidants, cinnamic acid, tacrine, Ellman's assay, nanocomposite, nanoparticles, chitosan, TPP.