QSAR study and VolSurf characterization of human intestinal absorption of drugs

The prediction of human intestinal absorption is a major goal in the design, optimization, and selection of candidates for the development of oral drugs. In this study, a computerized method (VolSurf with GRID) was used as a novel tool for predicting human intestinal absorption of test compound, and for determining the critical molecular properties needed for human intestinal absorption. The tested molecules consisted of 20 diverse drug-like compounds. Partial least squares (PIS) discriminant analysis was used to correlate the experimental data with the theoretical molecular properties of human intestinal absorption. A good correlation (r(2) = 0.95, q(2) = 0.86) between the molecular modeling results and the experimental data demonstrated that human intestinal absorption could be predicted from the three-dimensional (3D) molecular structure of a compound. Favorable structural properties identified for the potent intestinal absorption of drugs; included strong imbalance between the center of of a molecule and the barycentre of its hydrophilic and hydrophobic regions and a definitive hydrophobic region as well as less hydrogen bonding donors and acceptors in the molecule.