The MIA‐QSAR Method for the Prediction of Bioactivities of Possible Acetylcholinesterase Inhibitors

Abstract

This paper describes the use of the multivariate image analysis-quantitative structure-activity relationship (MIA-QSAR) methodology, which is a method capable of relating chemical structures with their biological activities. This in silico method has been shown to be extremely reliable and provides excellent results, even compared to those obtained by costly and time-consuming methods. Here, a class of acetylcholinesterase inhibitors was studied and three new compounds exhibiting high estimated pIC(50) values were found. They may be promising inhibitors for use in the treatment of Alzheimer's disease.

In Silico Studies in Drug Research Against Neurodegenerative Diseases

“…Bitencourt et al . [131] performed MIA-QSAR on a set of 34 compounds, including quaternary amines and carbamates with known anti-AChE activity. Structural analysis suggested the importance of a phenol group together with a carbamate scaffold in meta position of the benzene ring, to improve the AChE inhibitory activity.…”

Ten Years of the MIA-QSAR Strategy

“…From here on, these will be dominated as the traditional MIA-QSAR descriptors. These molecular descriptors (MDs) were successfully used in the modeling of numerous bioactivities such as: affinity to the dopamine D 2 receptor subtype (Freitas, Brown, & Martins, 2005), glycogen synthase kinase 3 (GSK-3) inhibitors (Goodarzi, Freitas, & Jensen, 2009), antimalarials (Cormanich, Freitas, & Rittner, 2011;Goodarzi & Freitas, 2011), anxiolytic agents receptor antagonists] (Bitencourt & Freitas, 2008), HIV reverse transcriptase inhibitors (Freitas, 2006;Goodarzi & Freitas, 2008;Goodarzi & Freitas, 2010a), phosphodiesterase type 5 (PDE-5) inhibitors (Antunes, Freitas, & Rittner, 2008), antifungals , peptides for treatment of dengue (Silla et al, 2011), anti-inflammatory agents (Lloret et al, 2009) and acetylcholinesterase inhibitors (Bitencourt, Freitas, & Rittner, 2012), among others. The traditional MIA-QSAR descriptors did not only find utility in the modeling of bioactivity endpoints; applications in spectroscopy (in the prediction of 13 C chemical shifts) (Goodarzi, Freitas, & Ramalho, 2009) and agrochemistry (in the modeling of the phytotoxicity and soil sorption profiles of herbicides) may be found in the literature (Bitencourt & Freitas, 2008;Freitas, Matias, Macedo, Freitas, & Venturin, 2013;Goodarzi & Freitas, 2010b).…”

Synthesis, molecular modeling studies, ADME prediction of arachidonic acid carbamate derivatives, and evaluation of their acetylcholinesterase activity

“…The cholinergic deficiency in Alzheimer's disease is related to a decrease in the concentration of ACh and its levels can be controlled via AChE inhibitors. An increase in the ACh concentration can result in the alleviation of the symptoms of several diseases such as Parkinson's, ataxia, senile dementia, myasthenia gravis, and Alzheimer's disease (Bitencourt, Freitas, & Rittner, ; Ehrenstein, Galdzicki, & Lange, ; Imramovský et al, ).…”