【摘要】 Caco-2单细胞层用于模拟或预测体内小肠吸收均较剥离的小肠膜效果好.利用偏最小二乘分析方法研究VolSurf参数与药物透过Caco-2单细胞层的渗透系数之间的定量结构-性质关系(QSPR),得到较好的结果(r2=0.95,q2=0.75).对其它类药物的预测结果表明,用结构不同的化合物所建立的模型对肽类药物以及同系物分子均有一定的预测能力,但是当分子的柔性键多,可能形成分子内氢键时,模型的预测能力大大下降.参数分析表明对Caco-2单细胞层渗透性高的药物分子必须具有合适的氢键给体和受体;分子内局部能量极小值越大,对渗透越有利;在一定范围内体积大且球形性高的分子对渗透有利.更多还原

【Abstract】 Caco-2 monolayer was used to simulate or predict the human intestinal absorption,and the effect was better than the isolated intestinal membrane.Quantitative structure-property relationship(QSPR) between the permeable coefficients of drugs across Caco-2 monolayer and VolSurf parameters was studied with partial least square analysis technique.Good result was obtained(r2 =0.95 and q2=0.75).The prediction results demonstrate that the model has some predictivity for peptide drugs and homologues.But the predictivity of the model decreases when more flexible bonds in the molecule result in intramolecular hydrogen bonds.The analysis of descriptors showed that the suitable hydrogen bond donors and acceptors are favorable to the permeability and the large local energy minima are beneficial to the permeability of drugs.To some extent,large volume and high globularity are favorable factors.更多还原