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

• Published in: European journal of medicinal chemistry Vol. 43; no. 8; pp. 1593 - 1602
• Main Authors: Duchowicz, Pablo R., Vitale, Martín G., Castro, Eduardo A., Autino, Juan C., Romanelli, Gustavo P., Bennardi, Daniel O.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Masson SAS 01.08.2008; Elsevier
• Subjects: Benzodiazepine receptor; Binding Sites; Biological and medical sciences; Dragon molecular descriptors; Flavone derivative; Flavonoids - chemistry; Flavonoids - metabolism; Flunitrazepam; GABA(A); Gabaergic and benzodiazepinic system; Medical sciences; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Protein Binding; QSAR; Quantitative Structure-Activity Relationship; Receptors, GABA-A - metabolism; Replacement method; GABA(A); QSAR; Dragon molecular descriptors; Flavone derivative; Benzodiazepine receptor; Replacement method; Flunitrazepam; Ligand; Prediction; Flavonoid; Modeling; Biological fixation; Structure activity relation; Molecular model; Flavone derivatives; Affinity; Gabaergic receptor A
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2007.11.009

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. QSAR analysis for the interaction of 78 flavone derivatives based on linear combinations of Dragon molecular descriptors. Results are compared with previously reported ones. [Display omitted]