THE SYNTHESIS AND POTENTIAL STUDY OF CHALCONE DERIVATIVES AS ANTIPSYCHOTIC AGENTS

• Main Author: Adirama, Azarya
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/85737
• Institution: Institut Teknologi Bandung

Psychosis is a mental condition that causes its sufferers to experience hallucinations and lose contact with reality. It has affected more than 2.6 million people in Indonesia. One of the causes of psychosis is the hyperactivity of dopaminergic transmissions at dopamine D2 receptors (DRD2). Psychosis can be exacerbated by the presence of reactive oxygen species (ROS), which can damage vital parts of the brain. Commercially available DRD2 inhibitors are known to cause severe side effects, which necessitates the search for DRD2 inhibitor compounds with antioxidant properties and less side effects. Chalcone derivatives have demonstrated radical scavenging properties, which are crucial for antipsychotic agents. Synthesis of chalcone derivatives is usually carried out using environmentally hazardous reagents and solvents, which further highlights the importance of an environmentally friendly synthesis method. This research focused on screening chalcone derivatives as potential DRD2 inhibitors and synthesizing the compound with the best potential using an environmentally friendly synthetic method. The screening of candidate compounds was conducted using AutoDock Vina and molecular dynamics simulations with GROMACS and the gmx_MMPBSA module to obtain the candidate compound with the best ?Gbinding value. The results of the molecular docking and molecular dynamics simulations showed that the TC2 compound (4´-hydroxychalcone) had the best ?Gbinding value, with a ?Gbinding value of -25.63 kcal/mol. From the docking simulation and MMPBSA results, it was found that the TC2 compound interacts with the active residues Cys118 and Ile184, as well as the Asp114, Ser193, and Ser197 residues, which play important roles in dopamine binding. The synthesis of the TC2 compound was then carried out in two stages: the preparation of the ionic liquid 1-decyl- 3-methylimidazolium bromide ([DMIm]Br) and the synthesis of the TC2 compound. The synthesis of [DMIm]Br was conducted using the MAOS (Microwave-Assisted Organic Synthesis) method at 50 °C and 200W for 60 minutes, while the TC2 compound was synthesized at 70 °C using reflux and MAOS methods with power variations of 50, 100, 150, and 200W in a basic environment and 10% (w/v) [DMIm]Br medium. The synthesis of [DMIm]Br yielded 87.17%. The optimal conditions found for the synthesis of TC2 were 100W, 70 °C, and 60 minutes, yielding 78.18%. This research demonstrates that all eight candidate compounds have potential as antipsychotic agents. Additional structural modifications to all eight candidate compounds remain necessary to minimize the conformational changes induced in DRD2 upon binding.