SYNTHESIS OF 6-AMINOPENICILLANIC ACID DERIVATIVES AND MOLECULAR DOCKING STUDY AS SARS-COV-2 MAIN PROTEASE (MPRO) INHIBITORS

• Main Author: Dwiputri Aminah, Agniya
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/68191
• Institution: Institut Teknologi Bandung

The acute respiratory syndrome caused by SARS-CoV-2 is still spreading around the world. There is currently no established clinical therapy to treat COVID-19. The two parts of this study were: (1) to find Schiff base compounds generated from 6-aminopenicillanic acid (6-APA) as potential anti-viral candidates against SARS-CoV-2 using the molecular docking method, and (2) laboratory synthesis. The docking parameter was obtained from the re-docking of the native ligand of the Mpro receptors (PDB ID: 7VH8) to the binding site of Mpro. The inhibitory potential of 6-APA derivatives was evaluated using Molegro Virtual Docker 7 and analyzed for its interaction with the active site of Mpro compared to nelfinavir as positive controls. Schiff bases with codes 7, 19, 32, 3, and 22 received the best docking score with rerank scores of ?108.53, ?108.53, ?106.59, ?104.51, ?103.40, and ?102.35 kcal/mol, respectively. Synthesis was carried out for the Schiff base compounds derived from 6-APA with benzaldehyde and salicylaldehyde, which interacts with crucial residues Cys 145 and His 41. These two compounds generated docking scores of ?88.35 kcal/mol dan ?83.52 kcal/mol, respectively. Schiff base from salicylaldehyde was purified using chromatography column gravity, with acetone as a solvent for the crude product before running by n-hexane: ethyl acetate (7:3) as the moving phase. The characterization of the synthesized product was carried out by 1H-NMR dan 13C-NMR spectroscopy. Schiff base obtained from the model reaction using aniline and salicylaldehyde as precursors produced a 54.17% yield. A proton imine is indicated by a chemical shift in the 1H-NMR spectrum at 8.6223 ppm. The purification procedures by recrystallization and chromatography did not result in isolating the Schiff base of 6-APA with benzaldehyde and salicylaldehyde. The 1H-NMR dan 13C-NMR spectra show that the contact between crude product and acetone results in an aldol reaction product of salicylaldehyde with acetone. Analysis using FTIR showed absorption in wave number 1624–1630 cm-1, indicating the C=N vibration of the crude product of the Schiff base synthesized from 6-APA with benzaldehyde.