从电性参数和分子体积预测药物的血浆蛋白结合率

PREDICTING DRUG-PROTEIN BINDING FROM ELECTRONIC PARAMETERS AND MOLECULAR VOLUME

目的:从电性参数和分子体积预测药物的血浆蛋白结合率。方法:根据半经验自洽场分子轨道AM1法得到的优化构型用Monte Carlo法计算得到分子体积。用逐步多元回归分析法建立从药物的电性参数、脂溶性和分子体积预测14种不同结构药物牛血清白蛋白结合率的数学模型。回归方程采用statistics60软件进行逐步多元回归分析得到。结果:13种不同结构药物的牛血清白蛋白结合率与分子酸碱性指示变量和分子体积有良好的相关性。回归方程为:%B(DAB)=187.42-39.47I+1.0×10-3V2-0.77V(n=13,R=0.9632)。结论:药物血浆蛋白结合率与分子的电性和分子体积密切相关。从分子电性参数和分子体积预测药物血浆蛋白结合率具有方便快捷的优点,可用于相关的药动学参数的研究。

Objective： To predict the percentage of drug - protein binding from electronic parameters and molecular volume. Methods：Moot Carlo method was used to obtain the molecular volume from their minimum energy conformations obtained from the optimization of the standard molecular geometry with the semiempirical self - consistent field molecular orbital calculation AM1 method. The stepwise multiple regression analysis was used to establish the model of predicting 14 drugs fraction bound to bovine serum albumin[ % B （DAB）] from electronic parameters, lipophilicity and molecular volume. The stepwise multiple regression analysis with statistics 60 was used to obtain the correlation equations. Results：Both indicator variables of acid and base and molecular volume are well correlated with the 13 drugs fraction bound to bovine serum albumin. The correlation equation is % B（DAB） = 187.42 - 39. 471 ＋ 1.0×10 - 3V2 - 0. 77V（ n = 13, R = 0. 9632 ）. Conclusion： Conclusion ： Drug - protein binding is closely related with the drug, s electronic parameters and molecular volume. The advantage of this research is that electronic parameters and molecular volume can be computed simply. It can also infer this method may be used to study other pharmaeokinetics parameters.