关键词: 人体小肠吸收（HIA）, 三维, VolSurf, 主成分分析（PCA）, 偏最小二乘法（PLS）

Abstract: The prediction of human intestinal absorption is a major goal in the design, optimization, and selection of candidates for the development of oral drugs. A computerized method (VolSurf/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 112 diverse drug-like compounds. Partial least squares discriminant analysis was used to correlate the experimental data with the theoretical molecular properties of human intestinal absorption. There was high consistency between two built models. A good correlation (r2=0.82, q2=0.67) between the molecular properties and the experimental data demonstrated that human intestinal absorption could be predicted from the three-dimensional molecular structure of a compound. Favorable structural properties identified for the potent intestinal absorption drugs included strong imbalance between the center of mass of a molecule and the barycenter of its hydrophilic and hydrophobic regions and a definitive hydrophobic region as well as less hydrogen bond donors on the molecule.

Key words: Human intestinal absorption (HIA), Three-dimension, VolSurf, Principal component analysis (PCA), Partial least squares (PLS)