2d Qsar and Docking Studies on Chalcone - Quinoxaline Variants – a Potential Target for Acetylcholinestrase Inhibitors

Abstract

AbstractThe Quantitative Structural Activity Relationship among 49 reported compounds containing chalcone derivatives as an acetylcholinesterase inhibitor. The acetylcholinesterase enzyme is the major leading threat to neurodegenerative disorders. The 2D QSAR study was done using QSARINS software. Model 2 was obtained as the best model with an r2value of 0.9398. The OECD principles were used to validate the model. The applicability domain of the model resulted in zero outliers. Based on the results of the QSAR study, 10 novel ligands possessing chalcones fused with quinoxaline were drawn. These 10 novel ligands showed class 5 toxicity, which was predicted using PROTOX II software. The ADME properties were also screened using preADMET. Molecular docking was performed between the 10 ligands and the acetylcholinesterase enzyme (PDB ID: 4EY7) using Autodock 4.0 softaware. 2D visualisation of drug interactions was also discussed. Compounds 4 and 5 with substitution of p-chloro and 2-bromo respectively demonstrated active binding to the catalytic anionic site and the peripheral anionic site, respectively. These results were compared with those of the standard drug, donepezil.