Prediction of human intestinal absorption from net polar atomic charges of drug molecules.
- Author:
Xu-chun FU
1
;
Shu-yu ZHAN
Author Information
- Publication Type:Journal Article
- MeSH: Adrenergic beta-Antagonists; pharmacokinetics; Biological Transport; physiology; Caco-2 Cells; Cell Membrane Permeability; physiology; Humans; Hydrogen Bonding; Intestinal Absorption; Models, Chemical; Molecular Structure; Pharmaceutical Preparations; metabolism; Regression Analysis
- From: Journal of Zhejiang University. Medical sciences 2006;35(2):199-203
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo predict human intestinal absorption and permeability coefficients in Caco-2 cell monolayers from net polar atomic charges of drug molecules.
METHODSThe net atomic charges and the volumes of drug molecules were obtained with the semiempirical self-consistent field molecular orbital calculation CNDO/2 method and Mont Carlo method respectively, using the minimum energy conformation obtained from the optimization of the standard molecular geometry with the molecular mechanics MM+ method. The stepwise multiple regression analysis was used to obtain the correlation equations.
RESULTBoth percent of human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules were well correlated with the sum of the net atomic charges of all hydrogen-bonding donors (sigmaQH) and the sum of the net atomic charges of all hydrogen-bonding acceptors (sigmaQN, 0). The more the net positive atomic charges of hydrogen-bonding donors and the net negative atomic charges of hydrogen-bonding acceptors, the less were the percent human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules.
CONCLUSIONDrug absorption in human intestines is closely related with its hydrogen-bonding potential. The drug molecules with weaker hydrogen-bonding potential have greater percent human intestinal absorption. The net polar atomic charges can be computed simply, so they can be used in high throughput screening of oral drugs.