3D-pharmacophores of flavonoid binding at the benzodiazepine GABA(A) receptor site using 4D-QSAR analysis.
4D-QSAR analysis was applied to a training set of 38 flavonoids where affinity constants, Ki, to the GABA(A) benzodiazepine receptor site, BzR, were determined. It was found that the -logKi values of the compounds are highly dependent on the size and electrostatics character of the substituents at the R(3') and R(6) positions of the flavonoid scaffold. Polar negative groups correctly embedded in the R(3') and/or R(6) substituents are predicted to increase -logKi values. A planar conformation of the flavonoid scaffold was found not to be a requirement for the flavonoids to be active. A test set of four compounds was used to evaluate the predictivity of the 4D-QSAR models.
Hong
Xuan
X
Laboratory of Molecular Modeling and Design (M/C 781), College of Pharmacy, The University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612-7231, USA.
Hopfinger
A J
AJ
D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008956:Models, Chemical; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000378:metabolism*
D005419:Flavonoids; D008024:Ligands; D011963:Receptors, GABA-A