Atom-based 3D-chiral quadratic indices. Part 3: prediction of the binding affinity of the stereoisomers of fenoterol to the beta(2) adrenergic receptor

作者：Castillo Garit Juan A^*; Garcia Domenech Ramon; Marrero Ponce Yovani; Torrens Francisco; Abad Concepcion

来源：Afinidad, 2011, 68(555): 334-340.

• non-stochastic and stochastic atom-based 3D-chiral quadratic indices
• beta(2)-adrenoceptor
• binding affinity
• fenoterol stereoisomer
• 3D-QSAR

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 beta(2)-adrenoceptor (beta(2)-AR). The prediction of beta(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 predictive power (assessed by the leave-one-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 prediction of biological activity, even in those studies in which the three-dimensional configuration of the chemicals play an important role in the bioactivity.

• 出版日期2011-10