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Three Dimensional Quantitative Structure Activity Relationship and Pharmacophore Modeling of Tacrine Derivatives as Acetylcholinesterase Inhibitors in Alzheimer's Treatment.
Med Chem. 2020; 16(2):155-168.MC

Abstract

BACKGROUND

Three dimensional quantitative structure activity relationship and pharmacophore modeling are studied for tacrine derivatives as acetylcholinesterase inhibitors.

METHODS

The three dimensional quantitative structure-activity relationship and pharmacophore methods were used to model the 68 derivatives of tacrine as human acetylcholinesterase inhibitors. The effect of the docked conformer of each molecule in the enzyme cavity was investigated on the predictive ability and statistical quality of the produced models.

RESULTS

The whole data set was divided into two training and test sets using hierarchical clustering method. 3D-QSAR model, based on the comparative molecular field analysis has good statistical parameters as indicated by q2 =0.613, r2 =0.876, and r2pred =0.75. In the case of comparative molecular similarity index analysis, q2, r2 and r2pred values were 0.807, 0.96, and 0.865 respectively. The statistical parameters of the models proved that the inhibition data are well fitted and they have satisfactory predictive abilities.

CONCLUSION

The results from this study illustrate the reliability of using techniques in exploring the likely bonded conformations of the ligands in the active site of the protein target and improve the understanding over the structural and chemical features of AChE.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Ansari F
Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Iran.
Ghasemi JB
Drug Design in Silico Lab, School of Sciences, Chemistry Faculty, University of Tehran, Tehran, Iran.
Niazi A
Department of Chemistry, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

MeSH

AcetylcholinesteraseAlzheimer DiseaseCholinesterase InhibitorsHumansMolecular Docking SimulationProtein ConformationQuantitative Structure-Activity RelationshipTacrine

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31092184

Citation

Ansari, Fatemeh, et al. "Three Dimensional Quantitative Structure Activity Relationship and Pharmacophore Modeling of Tacrine Derivatives as Acetylcholinesterase Inhibitors in Alzheimer's Treatment." Medicinal Chemistry (Shariqah (United Arab Emirates)), vol. 16, no. 2, 2020, pp. 155-168.
Ansari F, Ghasemi JB, Niazi A. Three Dimensional Quantitative Structure Activity Relationship and Pharmacophore Modeling of Tacrine Derivatives as Acetylcholinesterase Inhibitors in Alzheimer's Treatment. Med Chem. 2020;16(2):155-168.
Ansari, F., Ghasemi, J. B., & Niazi, A. (2020). Three Dimensional Quantitative Structure Activity Relationship and Pharmacophore Modeling of Tacrine Derivatives as Acetylcholinesterase Inhibitors in Alzheimer's Treatment. Medicinal Chemistry (Shariqah (United Arab Emirates)), 16(2), 155-168. https://doi.org/10.2174/1573406415666190513100646
Ansari F, Ghasemi JB, Niazi A. Three Dimensional Quantitative Structure Activity Relationship and Pharmacophore Modeling of Tacrine Derivatives as Acetylcholinesterase Inhibitors in Alzheimer's Treatment. Med Chem. 2020;16(2):155-168. PubMed PMID: 31092184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Three Dimensional Quantitative Structure Activity Relationship and Pharmacophore Modeling of Tacrine Derivatives as Acetylcholinesterase Inhibitors in Alzheimer's Treatment. AU - Ansari,Fatemeh, AU - Ghasemi,Jahan B, AU - Niazi,Ali, PY - 2018/09/22/received PY - 2019/03/23/revised PY - 2019/05/01/accepted PY - 2019/5/17/pubmed PY - 2020/9/15/medline PY - 2019/5/17/entrez KW - 3D-QSAR KW - Alzheimer disease KW - inhibitor KW - molecular docking KW - pharmacophore modeling KW - tacrine. SP - 155 EP - 168 JF - Medicinal chemistry (Shariqah (United Arab Emirates)) JO - Med Chem VL - 16 IS - 2 N2 - BACKGROUND: Three dimensional quantitative structure activity relationship and pharmacophore modeling are studied for tacrine derivatives as acetylcholinesterase inhibitors. METHODS: The three dimensional quantitative structure-activity relationship and pharmacophore methods were used to model the 68 derivatives of tacrine as human acetylcholinesterase inhibitors. The effect of the docked conformer of each molecule in the enzyme cavity was investigated on the predictive ability and statistical quality of the produced models. RESULTS: The whole data set was divided into two training and test sets using hierarchical clustering method. 3D-QSAR model, based on the comparative molecular field analysis has good statistical parameters as indicated by q2 =0.613, r2 =0.876, and r2pred =0.75. In the case of comparative molecular similarity index analysis, q2, r2 and r2pred values were 0.807, 0.96, and 0.865 respectively. The statistical parameters of the models proved that the inhibition data are well fitted and they have satisfactory predictive abilities. CONCLUSION: The results from this study illustrate the reliability of using techniques in exploring the likely bonded conformations of the ligands in the active site of the protein target and improve the understanding over the structural and chemical features of AChE. SN - 1875-6638 UR - https://www.unboundmedicine.com/medline/citation/31092184/Three_Dimensional_Quantitative_Structure_Activity_Relationship_and_Pharmacophore_Modeling_of_Tacrine_Derivatives_as_Acetylcholinesterase_Inhibitors_in_Alzheimer's_Treatment_ DB - PRIME DP - Unbound Medicine ER -