Prediction of the Binding Affinity between Fenoterol Derivatives and the b2 Adrenergic Receptor Using Atom-Based 3D-Chiral LinearIndices

The non-stochastic and stochastic atom-based 3D-chiral quadratic indices were applied to the study of the β 2 adrenoceptor (β2-AR) agonist effect (binding affinities) between a set of 26 stereoisomers of fenoterol, reported with this activity. Linear multiple regression analysis was carried out to predict the β 2 -AR binding affinities of the stereoisomers. Two statistically significant QSAR models, able to describe more than the 92% of the variance of the experimental binding affinities, were obtained using non-stochastic (R 2 = 0.924 and s = 0.21) and stochastic (R 2 = 0.92 and s = 0.22) 3D-chiral linear indices, respectively. The predictability and stability (robustness) of the obtained models (assessed by the leave-one-out cross-validation experiment) yielded values of q 2 = 0.893 (scv = 0.237) and q 2 = 0.886 (s cv = 0.245), respectively. The results obtained with our approach were slightly better than the results of a 3DQSAR model, 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 drug discovery of new lead compounds, even in those studies in which the three-dimensional configuration of the chemicals play an important role in the biological activity.