تاريخ مجلس الدراسات العليا

2019-09-09

اسم الطالب

روان أحمد حسين السحيمات

ملخص الرسالة

Alzheimer's disease (AD) is one of the prime causes of death among the older people worldwide. It is characterized by memory loss and cognitive impairment, which is caused primarily by damage to cholinergic neurons in the forebrain and hippocampus as well as a decrease in acetylcholine (ACh) levels; the second primary reason is Reactive oxygen species (ROS) trigger oxidative stress in many brain areas. The current treatment options for this neurodegenerative condition were mostly symptomatic. Quinazoline moiety has been shown to inhibit AChE enzyme and scavenge free radicals in several of studies. In this research a new hybrid compound 5 was synthesized with dual biological action to slow the progression of AD. Starting with N-methylisatoic anhydride, the final hybrid compound 5 was synthesized by four chemical reaction steps (71.35 % yield), all of which were monitored using TLC and GC-MS, and the final compound 5 was characterized using LC-MS, 1H-NMR and 13C-NMR. Compound 5 was evaluated for in vitro anti-cholinesterase activity using Ellman's assay and for free radical scavenging activity using DPPH assay. The obtained results of this study clearly show that compound 5 has a significant concentration-dependent inhibition activity of AChE enzyme with (IC50 = 11.89 ?g/ml, p<0.05) and significant antioxidant activity with (IC50 = 143.60 ?g/ml, p<0.05), comparable to standard drugs Galantamine (IC50 = 7.36 ?g/ml) and Ascorbic acid (IC50 = 42.96 ?g/ml), respectively. Key words: Alzheimer's disease, dementia, acetylcholine, acetylcholine esterase enzyme, oxidative stress, reactive oxygen species, antioxidants, tetrahydroquinazoline, ferulic acid, Ellman's assay, DPPH.