Number 1, Pages 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, Changhou Liu, Y Li, Y Wang, L Yang, S Zhang, C Liu, Y Li, Y Wang (+8 others)
2006 Internet Electronic Journal of Molecular Design   unpublished
Motivation. 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. Method. Pharmacophore modeling using DISCOtech and comparative molecular field analysis (CoMFA) methods were applied to the dataset to identify the pharmacophoric features as well as
more » ... eir 3D distribution. Results. 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 (R 2 > 0.9 and Q 2 > 0.5). Conclusions. All these models would be helpful for development of novel flavone-based P-gp inhibitors.