3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors: application of molecular field analysis

Patcharawee Nunthanavanit, N.G. Anthony, B.F. Johnston, S.P. Mackay, Jiraporn Ungwitayatorn

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 (r2cv), conventional r2, and predictive r2 (r2pred) 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.
Original languageEnglish
Pages (from-to)357-364
Number of pages7
JournalArchiv der Pharmazie
Volume341
Issue number6
DOIs
Publication statusPublished - 28 Apr 2008

Fingerprint

Chromones
HIV Protease Inhibitors
Quantitative Structure-Activity Relationship
Least-Squares Analysis
Guidelines
Human immunodeficiency virus 1 p16 protease

Keywords

  • alignment
  • chromone derivatives
  • HIV-1 protease
  • molecular field analysis (MFA)
  • 3D-QSAR

Cite this

Nunthanavanit, Patcharawee ; Anthony, N.G. ; Johnston, B.F. ; Mackay, S.P. ; Ungwitayatorn, Jiraporn. / 3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors: application of molecular field analysis. In: Archiv der Pharmazie. 2008 ; Vol. 341, No. 6. pp. 357-364.
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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 (r2cv), conventional r2, and predictive r2 (r2pred) 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.",
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3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors: application of molecular field analysis. / Nunthanavanit, Patcharawee; Anthony, N.G.; Johnston, B.F.; Mackay, S.P.; Ungwitayatorn, Jiraporn.

In: Archiv der Pharmazie, Vol. 341, No. 6, 28.04.2008, p. 357-364.

Research output: Contribution to journalArticle

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