3D-QSAR studies on chromone derivatives as HIV-1 protease inhibitors: application of molecular field analysis.
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 r(2) (r(2) (cv)), conventional r(2), and predictive r(2)(r(2)(pred)) values. The receptor-based MFA showed the best statistical results with r(2) (cv) = 0.789, r(2)= 0.886, and r(2)(pred) = 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.
Nunthanavanit
Patcharawee
P
Faculty of Pharmacy, Srinakharinwirot University, Nakhon Nayok, Thailand.
Anthony
Nahoum G
NG
Johnston
Blair F
BF
Mackay
Simon P
SP
Ungwitayatorn
Jiraporn
J
D000465:Algorithms; D001665:Binding Sites; D002867:Chromones / Q000737:chemistry*; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000737:chemistry*; D016018:Least-Squares Analysis; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship
D002867:Chromones; D017320:HIV Protease Inhibitors; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1