AMIDATION REACTION OF 6-AMINOPENICILLANIC ACID AND CYCLIC ANHYDRIDE AND IN SILICO STUDY OF ITS POTENTIAL AS INHIBITOR OF MPRO SARS-COV-2

• Main Author: Kofa, Rakatian
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/68075
• Institution: Institut Teknologi Bandung

Since its emergence in the first quarter of 2020, the SARS-CoV-2 virus has infected more than 6 million Indonesians. This virus spreads through droplets from people who have been infected, so the transmission rate of this virus is relatively high. One that is responsible for this viral infection is the Main protease (Mpro) SARS-CoV-2 (EC 3.4.22.69). The protein has Cys145 catalytic residue which plays a role in polyprotein cleavage in the replication process. Therefore, to decrease the activity of Mpro SARS-CoV-2, an inhibitor is needed to bind to catalytic residue. The inhibitor proposed in this study is a derivative compounds of 6-aminopenicillanic acid (6-APA) which has bioactivity. The search for potential inhibitors was carried out using molecular docking method. The molecular docking method is carried out using the Molegro Virtual Docker v7.0 software and the visualization is using the Molegro Molecular Viewer. Potential inhibitor candidates were selected based on the results of the lowest score and the presence of compound interactions with catalytic residues of Mpro. 19 compounds of 6-APA have been screened, one of the compounds that has potential as an Mpro inhibitor is 6-(2-carboxylbenzamido)penicillanic acid (2). Compound (2) has a score of -95.921 and it can interact with Cys145 through hydrogen bond interaction This research was continued in the laboratory by making a reaction model of phthalanilic acid (1) first using aniline and phthalic anhydride which were reacted in acetone. The results of the amidation reaction were analyzed using Thin Layer Chromatography (TLC) and Nuclear Magnetic Resonance (NMR) spectroscopy. The 13C-NMR spectrum showed a peak at a chemical shift of 167.48 ppm which indicated the presence of carbon amide. The resulting compound has a percentage yield of 18.65%. The subsequent amidation reaction was carried out using a different primary amine source, 6-APA. The low solubility of 6-APA in acetone necessitates the addition of Triethylamine (TEA) followed by an additional step of extraction and addition of acid. The reaction product has low solubility in water, DMSO, and other organic solvents, so analysis by NMR cannot be carried out. Analysis using FTIR shows that the N-H bending signal at the wave number of 1538 cm-1 belonging to 6-APA is lost and the C=O stretching signal appears from the product at the wave number of 1641 cm-1 originating from the secondary amide of the compound (2).