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Alignment-independent 3D-QSAR and molecular docking studies of tacrine-4-oxo-4H-Chromene hybrids as anti-Alzheimer's agents.
Comput Biol Chem. 2019 Jun; 80:463-471.CB

Abstract

A series of novel tacrine derivatives as multifunctional agents with potential inhibitory effects on both acetylcholinesterase(AChE) and butyrylcholinesterase (BuChE) enzymes for the treatment of Alzheimer's disease(AD), were applied to alignment independent 3D-QSAR methods using Pentacle software. In this studies, GRID-independent molecular descriptors (GRIND) analysis have been applied to characterize important interactions between enzymes and the studied compounds. Two H-bond acceptor groups as well as hydrophobic properties of tacrine rings for AChE and two H-bond acceptor on the carbonyl group of chromene and NH of amid group for BuChE, with positive effects on their inhibitory potency have been identified. The obtained 3D-QSAR models have been analyzed and validated. The statistical quality of the QSAR model for AChE, r2 = 0.87, q2 = 0.56 and for BuChE, r2 = 0.96, q2 = 0.70 was resulted. Using these models, novel structures have been designed and pIC50 of them were predicted. Molecular docking studies were also conducted on AChE (1ACJ) and BuChE (4BDS) and promising results in good agreement with 3D-QSAR studies were obtained.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Manouchehrizadeh E
Department of Chemistry, Khuzestan Science and Research Branch, Islamic Azad University, Ahvaz, Iran; Department of Chemistry, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran.
Mostoufi A
Department of Chemistry, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran; Marine Pharmaceutical Science Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: mostoufi-a@ajums.ac.ir.
Tahanpesar E
Department of Chemistry, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran.
Fereidoonnezhad M
Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

MeSH

AcetylcholinesteraseAlzheimer DiseaseAnimalsBenzopyransButyrylcholinesteraseCatalytic DomainCholinesterase InhibitorsDrug DesignHumansMolecular Docking SimulationMolecular StructureNootropic AgentsProtein BindingQuantitative Structure-Activity RelationshipTacrineTorpedo

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31170562

Citation

Manouchehrizadeh, Elham, et al. "Alignment-independent 3D-QSAR and Molecular Docking Studies of tacrine-4-oxo-4H-Chromene Hybrids as anti-Alzheimer's Agents." Computational Biology and Chemistry, vol. 80, 2019, pp. 463-471.
Manouchehrizadeh E, Mostoufi A, Tahanpesar E, et al. Alignment-independent 3D-QSAR and molecular docking studies of tacrine-4-oxo-4H-Chromene hybrids as anti-Alzheimer's agents. Comput Biol Chem. 2019;80:463-471.
Manouchehrizadeh, E., Mostoufi, A., Tahanpesar, E., & Fereidoonnezhad, M. (2019). Alignment-independent 3D-QSAR and molecular docking studies of tacrine-4-oxo-4H-Chromene hybrids as anti-Alzheimer's agents. Computational Biology and Chemistry, 80, 463-471. https://doi.org/10.1016/j.compbiolchem.2019.05.010
Manouchehrizadeh E, et al. Alignment-independent 3D-QSAR and Molecular Docking Studies of tacrine-4-oxo-4H-Chromene Hybrids as anti-Alzheimer's Agents. Comput Biol Chem. 2019;80:463-471. PubMed PMID: 31170562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alignment-independent 3D-QSAR and molecular docking studies of tacrine-4-oxo-4H-Chromene hybrids as anti-Alzheimer's agents. AU - Manouchehrizadeh,Elham, AU - Mostoufi,Azar, AU - Tahanpesar,Elham, AU - Fereidoonnezhad,Masood, Y1 - 2019/05/28/ PY - 2018/05/29/received PY - 2019/03/06/revised PY - 2019/05/23/accepted PY - 2019/6/7/pubmed PY - 2019/8/6/medline PY - 2019/6/7/entrez KW - 3D-QSAR KW - AChE KW - BuChE KW - Molecular docking SP - 463 EP - 471 JF - Computational biology and chemistry JO - Comput Biol Chem VL - 80 N2 - A series of novel tacrine derivatives as multifunctional agents with potential inhibitory effects on both acetylcholinesterase(AChE) and butyrylcholinesterase (BuChE) enzymes for the treatment of Alzheimer's disease(AD), were applied to alignment independent 3D-QSAR methods using Pentacle software. In this studies, GRID-independent molecular descriptors (GRIND) analysis have been applied to characterize important interactions between enzymes and the studied compounds. Two H-bond acceptor groups as well as hydrophobic properties of tacrine rings for AChE and two H-bond acceptor on the carbonyl group of chromene and NH of amid group for BuChE, with positive effects on their inhibitory potency have been identified. The obtained 3D-QSAR models have been analyzed and validated. The statistical quality of the QSAR model for AChE, r2 = 0.87, q2 = 0.56 and for BuChE, r2 = 0.96, q2 = 0.70 was resulted. Using these models, novel structures have been designed and pIC50 of them were predicted. Molecular docking studies were also conducted on AChE (1ACJ) and BuChE (4BDS) and promising results in good agreement with 3D-QSAR studies were obtained. SN - 1476-928X UR - https://www.unboundmedicine.com/medline/citation/31170562/Alignment_independent_3D_QSAR_and_molecular_docking_studies_of_tacrine_4_oxo_4H_Chromene_hybrids_as_anti_Alzheimer's_agents_ DB - PRIME DP - Unbound Medicine ER -