Document Report Card

ID: ALA1134495

Journal: J Med Chem

Title: 3D-QSAR model of flavonoids binding at benzodiazepine site in GABAA receptors.

Authors: Huang X, Liu T, Gu J, Luo X, Ji R, Cao Y, Xue H, Wong JT, Wong BL, Pei G, Jiang H, Chen K.

Abstract: With flavone as a structural template, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies and ab initio calculations were performed on a series of flavonoids. A reasonable pharmacophore model was built through CoMFA, CoMSIA, and HQSAR analyses and electrostatic potential calculations. A plausible binding mode for flavonoids with GABA(A) receptors was rationalized. On the basis of the commonly recognized binding site, the specific S1 and S2 subsites relating to substituent positions were proposed. The different binding affinities could be explained according to the frontier orbitals and electrostatic potential (ESP) maps. The ESP could be used as a novel starting point for designing more selective BZ-binding-site ligands.

CiteXplore: 11384234

DOI: 10.1021/jm000557p