Prospective atom-based 3D-QSAR model prediction, pharmacophore generation, and molecular docking study of carbamate derivatives as dual inhibitors of AChE and MAO-B for Alzheimer’s disease

Abstract

Carbamates are well known for AChE as well as MAO inhibition. In this study, atom-based 3D-QSAR model generation, virtual screening, and molecular docking studies were performed for a known series of 31 carbamate derivatives. The best hypothesis yielded four different pharmacophoric features with statistically significant 3D-QSAR model (correlation coefficient of R2 = 0.994 for training set molecules and very good predictive powers with Q2 and Pearson-R were 0.60 and 0.91, respectively). By virtual screening done against Schrodinger database, we identified 11 distinct drug-like molecules binding to both targets AChE and MAO-B efficiently. This generated 3D-QSAR hybrid model for dual enzymes provides basis for new structural scaffold would serve as building blocks in designing drug-like molecules for Alzheimer’s disease.