Atom-based 3D-chiral quadratic indices. Part 3: Prediction of the binding affinity of the stereoisomers offenoterol to the β 2 adrenergic receptor

Abstract:

The non-stochastic and stochastic atom-based three dimensional (3D)-chiral quadratic indices are applied to predict the binding affinities of 26 stereoisomers of fenoterol with the β <inf>2</inf>-adrenoceptor (β <inf>2</inf>-AR). The prediction of β <inf>2</inf>-AR binding affinities of the stereoisomers is carried out by multiple linear regression analysis. Two statistically significant QSAR models are obtained when non-stochastic (R ² = 0.941 and s = 0.19) and stochastic (R ²= 0.947 and s = 0.18) 3D-chiral quadratic indices are used. These models show adequate predictive power (assessed by the leaveone-out cross-validation experiment), yielding values of q ² = 0.909 (s <inf>Cv</inf>= 0.219) and q ² = 0.917 (s <inf>cv</inf> = 0.208), respectively. These models compare favorably with a 3D-QSAR equation obtained with the CoMFA method (R ² = 0.920, q ² = 0.847 and s <inf>cv</inf> = 0.309). The results of our work demonstrate the usefulness of our topological approach for the prediction of biological activity, even in those studies in which the three-dimensional configuration of the chemicals play an important role in the bioactivity.

Año de publicación:

2011

Keywords:

• Binding affinity
• Fenoterol stereoisomer
• β -adrenoceptor 2
• 3D-QSAR
• Non-stochastic and stochastic atom-based 3D-chiral quadratic indices
• β 2-adrenoceptor

Fuente:

scopus

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