QSAR modeling of the interaction of flavonoids with GABA(A) receptor

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 Structure–Activity 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.

Graphical abstractQSAR analysis for the interaction of 78 flavone derivatives based on linear combinations of Dragon molecular descriptors. Results are compared with previously reported ones.Figure optionsDownload full-size imageDownload as PowerPoint slide