QSAR Study and VolSurf Characterization of Human Intestinal Absorption of Druge

The prediction of human intestinal absorption is a major goal in the design,optimization,and selection of candidates for the develoment 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(PLS) 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 structureal properties identified for the potent intestinal absorption of drugs included strong imbalance between the center of mass 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.

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 (PLS) discriminate analysis was used to correlate the experimental data with the theoretical molecular properties of human intestinal absorption. A good correlation (r² = 0.95, q² = 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 mass 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.