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Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives.
Arch Pharm Res. 2016 May; 39(5):591-602.AP

Abstract

Acetylcholinesterase (AChE) is an important enzyme in the pathogenesis of Alzheimer's disease (AD). Comparative quantitative structure-activity relationship (QSAR) analyses on some huprines inhibitors against AChE were carried out using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) methods. Three highly predictive QSAR models were constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have values of r (2) = 0.988, q (2) = 0.757, ONC = 6; r (2) = 0.966, q (2) = 0.645, ONC = 5; and r (2) = 0.957, q (2) = 0.736, ONC = 6. The predictabilities were validated using an external test sets, and the predictive r (2) values obtained by the three models were 0.984, 0.973, and 0.783, respectively. The analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the AChE to further understand the vital interactions between huprines and the protease. On the basis of the QSAR study, 14 new potent molecules have been designed and six of them are predicted to be more active than the best active compound 24 described in the literature. The final QSAR models could be helpful in design and development of novel active AChE inhibitors.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Zhang S
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
Hou B
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
Yang H
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zuo Z
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. zuozhili@mail.kib.ac.cn. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. zuozhili@mail.kib.ac.cn.

MeSH

AlkaloidsAminoquinolinesCholinesterase InhibitorsDrug DesignHeterocyclic Compounds, 4 or More RingsMolecular Docking SimulationMolecular StructurePredictive Value of TestsQuantitative Structure-Activity RelationshipSesquiterpenesTacrine

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26832327

Citation

Zhang, Shuqun, et al. "Design and Prediction of New Acetylcholinesterase Inhibitor Via Quantitative Structure Activity Relationship of Huprines Derivatives." Archives of Pharmacal Research, vol. 39, no. 5, 2016, pp. 591-602.
Zhang S, Hou B, Yang H, et al. Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives. Arch Pharm Res. 2016;39(5):591-602.
Zhang, S., Hou, B., Yang, H., & Zuo, Z. (2016). Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives. Archives of Pharmacal Research, 39(5), 591-602. https://doi.org/10.1007/s12272-016-0709-9
Zhang S, et al. Design and Prediction of New Acetylcholinesterase Inhibitor Via Quantitative Structure Activity Relationship of Huprines Derivatives. Arch Pharm Res. 2016;39(5):591-602. PubMed PMID: 26832327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives. AU - Zhang,Shuqun, AU - Hou,Bo, AU - Yang,Huaiyu, AU - Zuo,Zhili, Y1 - 2016/02/01/ PY - 2015/07/20/received PY - 2016/01/14/accepted PY - 2016/2/3/entrez PY - 2016/2/3/pubmed PY - 2017/2/9/medline KW - AChE KW - AD KW - CoMFA KW - CoMSIA KW - HQSAR KW - Huprines inhibitors SP - 591 EP - 602 JF - Archives of pharmacal research JO - Arch Pharm Res VL - 39 IS - 5 N2 - Acetylcholinesterase (AChE) is an important enzyme in the pathogenesis of Alzheimer's disease (AD). Comparative quantitative structure-activity relationship (QSAR) analyses on some huprines inhibitors against AChE were carried out using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) methods. Three highly predictive QSAR models were constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have values of r (2) = 0.988, q (2) = 0.757, ONC = 6; r (2) = 0.966, q (2) = 0.645, ONC = 5; and r (2) = 0.957, q (2) = 0.736, ONC = 6. The predictabilities were validated using an external test sets, and the predictive r (2) values obtained by the three models were 0.984, 0.973, and 0.783, respectively. The analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the AChE to further understand the vital interactions between huprines and the protease. On the basis of the QSAR study, 14 new potent molecules have been designed and six of them are predicted to be more active than the best active compound 24 described in the literature. The final QSAR models could be helpful in design and development of novel active AChE inhibitors. SN - 1976-3786 UR - https://www.unboundmedicine.com/medline/citation/26832327/Design_and_prediction_of_new_acetylcholinesterase_inhibitor_via_quantitative_structure_activity_relationship_of_huprines_derivatives_ DB - PRIME DP - Unbound Medicine ER -