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

Molecules

Simone Decembrino de Souza⁴  Alessandra Mendon๺ Teles de Souza⁴  Ana Carolina Corrສ de Sousa⁴  Ana Carolina Rennó Sodero⁴  Lྫྷio Mendes Cabral¹  Magaly Girão Albuquerque³  Helena Carla Castro² 

[1] Laboratory of Industrial Pharmaceutical Technology (LabTIF), Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21941-590, RJ, Brazil;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;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;Laboratory of Molecular Modeling & QSAR-3D (ModMolQSAR), Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21949-900, RJ, Brazil

关键词: HQSAR;    acetylcholinesterase;    butyrylcholinesterase;    Alzheimer’s disease (AD);   

DOI  :  10.3390/molecules17089529

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.