QSAR Modeling of the Interaction of Flavonoids with GABA(A) Receptor

DUCHOWICZ, P. R.; VITALE, M. G.; CASTRO, E. A.; AUTINO, J. C.; ROMANELLI, G. P.; BENARDI, D. O.

European Journal of Medicinal Chemistry

Año: 2008 vol. 43 p. 1593 - 1602

0223-5234

Experimentally assigned values to binding affinity constants of flavonoid ligands towards the benzodiazepine site of the GABA(A) receptor complex were compiled from several publications, and enabled to perform a predictive analysis based on Quantitative StructureeActivity Relationships (QSAR). The best linear model established on 78 molecular structures incorporated four molecular descriptors, selected from more than a thousand of geometrical, topological, quantum-mechanical and electronic types of descriptors and calculated by Dragon software. An application of this QSAR equation was performed by estimating the binding affinities for some newly synthesized flavonoids displaying 2-,7-substitutions in the benzopyrane backbone which still do not have experimentally measured potencies.