title: Hologram QSAR models of 4-[(diethylamino)methyl]-phenol inhibitors of acetyl/butyrylcholinesterase enzymes as potential anti-Alzheimer agents.
abstract: Hologram QSAR models were developed for a series of 36 inhibitors (29 training set and seven test set compounds) of acetyl/butyrylcholinesterase (AChE/BChE) enzymes, an attractive molecular target for Alzheimer's disease (AD) treatment. The HQSAR models (N = 29) exhibited significant cross-validated (AChE, q2 = 0.787; BChE, q2 = 0. 904) and non-cross-validated (AChE, r2 = 0.965; BChE, r2= 0.952) correlation coefficients. The models were used to predict the inhibitory potencies of the test set compounds, and agreement between the experimental and predicted values was verified, exhibiting a powerful predictive capability. Contribution maps show that structural fragments containing aromatic moieties and long side chains increase potency. Both the HQSAR models and the contribution maps should be useful for the further design of novel, structurally related cholinesterase inhibitors.
authors.affiliation: Laboratory of Molecular Modeling & QSAR-3D (ModMolQSAR), Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21949-900, RJ, Brazil.
authors.forename: Simone Decembrino
authors.initials: SD
authors.lastname: de Souza
authors.forename: Alessandra Mendonça Teles
authors.initials: AM
authors.lastname: de Souza
authors.forename: Ana Carolina Corrêa
authors.initials: AC
authors.lastname: de Sousa
authors.forename: Ana Carolina Rennó
authors.initials: AC
authors.lastname: Sodero
authors.forename: Lúcio Mendes
authors.initials: LM
authors.lastname: Cabral
authors.forename: Magaly Girão
authors.initials: MG
authors.lastname: Albuquerque
authors.forename: Helena Carla
authors.initials: HC
authors.lastname: Castro
authors.forename: Carlos Rangel
authors.initials: CR
authors.lastname: Rodrigues
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006696:Holography; D006801:Humans; D008958:Models, Molecular; D019800:Phenol / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D019800:Phenol; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase