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Molecules 2012, 17(8), 9529-9539; doi:10.3390/molecules17089529
Article

Hologram QSAR Models of 4-[(Diethylamino)methyl]-phenol Inhibitors of Acetyl/Butyrylcholinesterase Enzymes as Potential Anti-Alzheimer Agents

1, 1, 1, 1, 2, 3,* , 4 and 1,*
1 Laboratory of Molecular Modeling & QSAR-3D (ModMolQSAR), Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21949-900, RJ, Brazil 2 Laboratory of Industrial Pharmaceutical Technology (LabTIF), Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21941-590, RJ, Brazil 3 Laboratory of Molecular Modeling (LabMMol), Program of Post-Graduation in Chemistry (PPGQu) Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21949-900, RJ, Brazil 4 Laboratory of Antibiotics, Biochemistry, Education and Molecular Modeling (LABiEMol), Institute of Biology (IB), Fluminense Federal University (UFF), Campus of Valonguinho, Niterói, 24210-130, RJ, Brazil
* Authors to whom correspondence should be addressed.
Received: 25 June 2012 / Revised: 17 July 2012 / Accepted: 26 July 2012 / Published: 9 August 2012
(This article belongs to the Special Issue QSAR and Its Applications)
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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.
Keywords: HQSAR; acetylcholinesterase; butyrylcholinesterase; Alzheimer’s disease (AD) HQSAR; acetylcholinesterase; butyrylcholinesterase; Alzheimer’s disease (AD)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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de Souza, S.D.; de Souza, A.M.T.; de Sousa, A.C.C.; Sodero, A.C.R.; Cabral, L.M.; Albuquerque, M.G.; Castro, H.C.; Rodrigues, C.R. Hologram QSAR Models of 4-[(Diethylamino)methyl]-phenol Inhibitors of Acetyl/Butyrylcholinesterase Enzymes as Potential Anti-Alzheimer Agents. Molecules 2012, 17, 9529-9539.

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