Chemometric Modeling of Structurally Diverse Carbamates for the Inhibition of Acetylcholinesterase (AChE) Enzyme in Alzheimer's Disease

Abstract

In this research, we have developed two-dimensional quantitative structure-activity relationship (2D-QSAR) and group-based QSAR (GQSAR) models employing a dataset of 78 carbamate derivatives (acetylcholinesterase enzyme inhibitors). The developed models were validated using various stringent validation parameters. From the insights obtained from the developed 2D-QSAR and GQSAR models, we have found that the structural features appearing in the models are responsible for the enhancement of the inhibitory activity against the AChE enzyme. Furthermore, we have performed the pharmacophore modeling to unveil the structural requirements for the inhibitory activity. Additionally, molecular docking studies were performed to understand the molecular interactions involved in binding, and the results are then correlated with the requisite structural features obtained from the QSAR and pharmacophore models.