Article ID Journal Published Year Pages File Type
7832021 Acta Physico-Chimica Sinica 2007 7 Pages PDF
Abstract
A three-dimensional pharmacophore model was developed for a considerable number of pyrrolidine-based and butane-based chemokine (C-C motif) receptor 5 (CCR5) antagonists, which can block the entry of human immunodeficiency virus type 1 (HIV-1) by inhibiting the interaction of HIV-1 envelope protein and CCR5. The pharmacophore model was generated using a training set consisting of 25 carefully selected antagonists with the diverse molecular architecture and bioactivity, as required by the Catalyst/HypoGen program. The activity of the training set molecules expressed in IC50 (half-inhibitory concentration) covered from 0.06 to 10000 nmol·L-1. The most predictive pharmacophore model (Hypo 1), consisting of two positive ionizable points and three hydrophobic groups, had a correlation of 0.924 and a root mean square of 1.068, and a cost difference of 63.67 bits between the null cost and the total cost. The model was applied in predicting the activity of 74 compounds as a test set. The results indicated that the model was able to provide clear guidelines and accurate activity prediction for novel antagonist design.
Related Topics
Physical Sciences and Engineering Chemistry Physical and Theoretical Chemistry
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