Hologram QSAR Models of 4-[(Diethylamino)methyl]-phenol Inhibitors of Acetyl/Butyrylcholinesterase Enzymes as Potential Anti-Alzheimer Agents |
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Authors: | Simone Decembrino de Souza Alessandra Mendonça Teles de Souza Ana Carolina Corrêa de Sousa Ana Carolina Rennó Sodero Lúcio Mendes Cabral Magaly Girão Albuquerque Helena Carla Castro Carlos Rangel Rodrigues |
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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. magaly@iq.ufrj.br. |
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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. |
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