Hydrophobic moments as physicochemical descriptors in structure-activity relationship studies of P-glycoprotein inhibitors

摘要

Lipophilicity is one of the major determining physicochemical descriptors for P-glycoprotein (P-gp) inhibitory activity. In order to consider lipophilicity as a space directed property, we apply the concept of hydrophobic moments on a set of propafenone-type inhibitors of P-glycoprotein and use them as descriptors in QSAR analyses. While the 0th moment is the sum of the atomic hydrophobicity coefficients, which is a measure for the total hydrophobicity of the molecule, the 1st moment (or hydrophobic dipole) is a measure for the asymmetry of the distribution of hydrophobicities and therefore is analogous to the electrostatic dipole. The use of these hydrophobic dipole moments as independent variables remarkably improved the predictive power of QSAR models obtained.