SYNTHESIS OF QUINAZOLINONE DERIVATIVES AS ACETYLCHOLINESTERASE INHIBITORS

• Main Author: Carnelian Christy, Angellyn
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/83117
• Institution: Institut Teknologi Bandung

Alzheimer is a neurodegenerative disorder that primarily affects older adults. This disease is caused by a decrease in the production of acetylcholine, a crucial neurotransmitter involved in memory function. The presence of acetylcholinesterase, an enzyme capable of hydrolyzing acetylcholine, leads to a further decrease in the concentration of this neurotransmitter. This condition results in memory loss and other cognitive function impairments in patients with Alzheimer's disease. Therefore, Alzheimer's disease can be treated using compounds that inhibit the activity of acetylcholinesterase. Several existing acetylcholinesterase inhibitors, such as tacrine, donepezil, rivastigmine, and galantamine, have significant side effects and do not fully treat Alzheimer's disease. This has led to ongoing research into acetylcholinesterase inhibitors. One compound with potential as an acetylcholinesterase inhibitor is quinazolinone. Previous studies have shown that quinazolinone derivatives have better inhibitory effects on acetylcholinesterase compared to existing Alzheimer's disease medications. The main ring structure of quinazolinone as an acetylcholinesterase inhibitor is a cyclic ring containing nitrogen atoms and aromatic substituents. In this study, quinazolinone derivatives were successfully synthesized with various types of alcohol substituents at position C-7. The synthesis was done through three steps: cyclization, nitration, and substitution. The synthesized products were characterized using mass spectrometry and nuclear magnetic resonance spectroscopy, and their activities against acetylcholinesterase were tested using the modified Ellman’s method. This study successfully synthesized ten quinazolinone derivatives, consisting of five new compounds and five previously reported ones. The inhibition test results showed that seven compounds had inhibitory abilities above 70%, with 7-propoxy-6- nitroquinazolin-4(3H)-one and 7-(2-ethoxyethoxy)-6-nitroquinazolin-4(3H)-one having strong inhibitory activities with IC50 values of 3.24 ± 0.06 ?M and 3.79 ± 0.36 ?M, respectively. The kinetic test results showed that these two compounds have a mixed-type inhibition mechanism. Therefore, quinazolinone derivatives substituted with alkoxy groups at the C-7 position have potential for further investigation as acetylcholinesterase inhibitors.