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Atom-based 3D-chiral quadratic indices. Part 3: Pbkp_rediction of the binding affinity of the stereoisomers offenoterol to the β <inf>2</inf> adrenergic receptor

Abstract:

The non-stochastic and stochastic atom-based three dimensional (3D)-chiral quadratic indices are applied to pbkp_redict the binding affinities of 26 stereoisomers of fenoterol with the β 2-adrenoceptor (β 2-AR). The pbkp_rediction of β 2-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 pbkp_redictive power (assessed by the leaveone-out cross-validation experiment), yielding values of q 2 = 0.909 (s Cv= 0.219) and q 2 = 0.917 (s cv = 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 cv = 0.309). The results of our work demonstrate the usefulness of our topological approach for the pbkp_rediction of biological activity, even in those studies in which the three-dimensional configuration of the chemicals play an important role in the bioactivity.