Publication: 3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors: Application of molecular field analysis
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Issued Date
2008
Resource Type
File Type
application/pdf
ISSN
3656233
Other identifier(s)
2-s2.0-50949092681
Rights Holder(s)
Scopus
Bibliographic Citation
Archiv der Pharmazie. Vol 341, No.6 (2008), p.357-364
Suggested Citation
Nunthanavanit P., Anthony N.G., Johnston B.F., Mackay S.P., Ungwitayatorn J. 3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors: Application of molecular field analysis. Archiv der Pharmazie. Vol 341, No.6 (2008), p.357-364. doi:10.1002/ardp.200700229 Retrieved from: https://hdl.handle.net/20.500.14740/3970
Abstract
Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for chromone derivatives against HIV-1 protease using molecular field analysis (MFA) with genetic partial least square algorithms (G/PLS). Three different alignment methods: field fit, pharmacophore-based, and receptor-based were used to derive three MFA models. All models produced good predictive ability with high cross-validated r2 (r2 cv), conventional r2, and predictive r2 (r 2pred) values. The receptor-based MFA showed the best statistical results with r2cv = 0.789, r2 = 0.886, and r2pred = 0.995. The result obtained from the receptor-based model was compared with the docking simulation of the most active compound 21 in this chromone series to the binding pocket of HIV-1 protease (PDB entry 1AJX). It was shown that the MFA model related well with the binding structure of the complex and can provide guidelines to design more potent HIV-1 protease inhibitors. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.
Subject(s)
Chromone derivative
Proteinase inhibitor
Chromone derivative
P16 protease, Human immunodeficiency virus 1
Proteinase
Proteinase inhibitor
Article
Drug protein binding
Molecular model
Pharmacophore
Predictive validity
Priority journal
Quantitative structure activity relation
Simulation
Three dimensional imaging
Algorithm
Binding site
Chemical structure
Chemistry
Conformation
Drug design
Regression analysis
Algorithms
Binding Sites
Chromones
Drug Design
HIV Protease
HIV Protease Inhibitors
Least-Squares Analysis
Models, Molecular
Molecular Conformation
Quantitative Structure-Activity Relationship
Proteinase inhibitor
Chromone derivative
P16 protease, Human immunodeficiency virus 1
Proteinase
Proteinase inhibitor
Article
Drug protein binding
Molecular model
Pharmacophore
Predictive validity
Priority journal
Quantitative structure activity relation
Simulation
Three dimensional imaging
Algorithm
Binding site
Chemical structure
Chemistry
Conformation
Drug design
Regression analysis
Algorithms
Binding Sites
Chromones
Drug Design
HIV Protease
HIV Protease Inhibitors
Least-Squares Analysis
Models, Molecular
Molecular Conformation
Quantitative Structure-Activity Relationship