A QSAR study using MTD method and Dragon descriptors for a series of selective ligands of α2C adrenoceptor.

ABSTRACT

A QSAR (quantitative structure-activity relationship) analysis of the binding affinities for a series of 43 quinoline derivatives active against the alpha2C adrenergic receptor was performed. Multiple linear regressions (MLR) were obtained using the minimum topological difference (MTD) descriptor and various descriptors which were calculated with Dragon3.0. The variable selection was performed either through the forward stepwise method or backward stepwise combined with forward stepwise methods, providing two satisfactory models. The first one, obtained as a result of the forward stepwise method, contains MTD, Mor24v, MATS5m, MATS7m, G3m, L1s, G_N_N descriptors, while the other one obtained through the combination of backward and forward stepwise methods contains the following descriptors MTD, ZM2V, X5V, IC5, MATS4v, and E2u. Both models highlight the importance of steric interactions and can be used as tools for predicting the binding affinity of related compounds.