Views: 307 Downloads: 47

Abstract

Different compounds of 4-amino antipyrine (4-Aminophenazone) were synthesized through two lines: the first line was through the reaction of the raw material with phenacyl bromide derivatives, which are three derivatives with the presence of triethylamine as a catalyst, and the second line was through the reaction of the starting material with two derivatives of benzoyl chloride one of the compound Pre-factory (B1). The results were analyzed through FTIR, HNMR, and ¹³CNMR, and molecular docking was performed, and the results were confirmed. The results showed that the compounds act as inhibitors of the COMT enzyme, but to a lesser extent than the basic substance, tolcapone. This work involved molecular docking of synthesized molecules with the COMT enzyme, yielding favorable ratings in comparison to the co-crystal ligand and tolcapone. The molecule exhibiting the highest docking score was chosen for molecular dynamics (MD) simulation utilizing the GROMACS program. The simulation results were evaluated using several parameters, including RMSD, SASA, RMSF, and Rg. The RMSD study demonstrated consistent ligand binding throughout the simulation duration. The SASA results indicated uniform solvent accessibility, whereas the RMSF emphasized areas of flexibility within the protein. The Rg values indicated the overall compactness and stability of the protein-ligand complex. The results indicate that the synthesized chemical demonstrates significant binding stability and interaction with the COMT enzyme, necessitating additional research for possible therapeutic uses.

Keywords: 4-Aminophenazone, Molecular docking, Molecular dynamics, COMT enzyme

Citation Formats: