Abstract

Quantitative structure activity relationship approach using stepwise regression analysis was applied to a series of 4-quinolone derivatives as high-affinity ligands at the benzodiazepine site of brain GABAA receptors. For the purpose 25 compounds were used to develop models. Statistically significant equations were obtained with high squared correlation coefficient (r2=0.8761, 0.9295 and 0.8705) and low root mean square error (RMSE=0.4844, 0.3894 and 0.4952). The robustness of the model was confirmed with the help of leave one out cross validation method which exhibited high r2 cv values (r2 cv=0.7875, 0.8263 and 0.7927). A good correlation of various molecular shape parameters, like ovality, Szeged index, and energy of the molecule with the GABAA affinity was achieved.

Keywords: GABA, QSAR, leave one out, molecular descriptors, stepwise regression analysis