In silico modeling for dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes in Alzheimer's disease.

In silico modeling for dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes in Alzheimer's disease. Comput Biol Chem. 2020 Aug 05;88:107355 Authors: Kumar V, Saha A, Roy K Abstract In this research, we have implemented two-dimensional quantitative structure-activity relationship (2D-QSAR) modeling using two different datasets, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzyme inhibitors. A third dataset has been derived based on their selectivity and used for the development of partial least squares (PLS) based regression models. The developed models were extensively validated using various internal and external validation parameters. The features appearing in the model against AChE enzyme suggest that a small ring size, higher number of -CH2- groups, higher number of secondary aromatic amines and higher number of aromatic ketone groups may contribute to the inhibitory activity. The features obtained from the model against BuChE enzyme suggest that the sum of topological distances between two nitrogen atoms, higher number of fragments X-C(=X)-X, higher number of secondary aromatic amides, fragment R--CR-X may be more favorable for inhibition. The features obtained from selectivity based model suggest that the number of aromatic ethers, unsaturation content relative to the molecular size and molecular shape may be more specific for the inhibition of the AChE enzyme in comp...
Source: Computational Biology and Chemistry - Category: Bioinformatics Authors: Tags: Comput Biol Chem Source Type: research