Authors:
Érica Cristina Moreno Nascimento
and
João Batista Lopes Martins
Affiliation:
Universidade de Brasília, Brazil
Keyword(s):
Alzheimer disease, AChE Inhibitors, DFT, Multivariate analysis, PCA.
Related
Ontology
Subjects/Areas/Topics:
Bioinformatics
;
Biomedical Engineering
;
Biostatistics and Stochastic Models
;
Pharmaceutical Applications
;
Structural Bioinformatics
Abstract:
Alzheimer's disease (AD) is a degenerative dementia. The causes of AD are not well determined, and the most popular strategy for AD treatment is the cholinergic hypothesis, that consists in the use of drugs with an inhibitory effect on acetylcholinesterase (AChE) enzyme, to prevent the decrease on the neurotransmitter (acetylcholine) concentration in synaptic clefts. Structural, electronic and spatial parameters of 10 drugs with known inhibitory effect on AChE (AChEI) were determined. The parameter values were obtained by means of calculations at B3LYP/6-31+G(d,p) level. The multivariate analysis of principal components (PCA) method was applied to 18 parameters to determine the pharmacophoric profile. PCA study was performed to reduce the sample space of properties and get the ones that are major AChEI components.