|
Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. January 2006, Volume 5, Number 1, 1-12 |
Structural Determinants of Flavones Interacting with the C-Terminal
Nucleotide-Binding Domain as P-Glycoprotein Inhibitors
Yan Li, Yonghua Wang, Ling Yang, Shuwei Zhang, and Changhou Liu
Internet Electron. J. Mol. Des. 2006, 5, 1-12
|
Abstract:
To determine the structural features of flavones required for the
reversal of P-glycoprotein (P-gp) mediated multidrug resistance,
we studied the quantitative structure-activity relationships
(QSAR) of a series of flavones specifically binding to the C-terminal
nucleotide-binding domain of mouse P-gp.
Pharmacophore modeling using DISCOtech and comparative
molecular field analysis (CoMFA) methods were applied to the
dataset to identify the pharmacophoric features as well as their
3D distribution. The proposed pharmacophore model including
two hydrophobic and two hydrogen bond acceptor sites
characterizes the necessary structural features of flavone
inhibitors. CoMFA was also applied to the dataset, resulting in
several 3D-QSAR models with good statistical indices (R2 > 0.9
and Q2 > 0.5). All these models would be helpful for
development of novel flavone-based P-gp inhibitors.
|