1-取代-2-氨基苯并咪唑化合物QSAR研究

利用量子化学程序计算了8个1-取代-2-氨基苯并咪唑化合物的结构和量子化学参数(最高充满轨道能量、最低空轨道能量、水化能、极化率、生成热、N1原子静电势、摩尔折射率等),并分别对雌、雄小鼠急性毒性进行了定量结构-活性相关(QSARs)分析。结果表明,正辛醇-水分配系数、最低空轨道能量、极化率、水化能4个参数共同构建的模型准确性最高,解决了化合物苯环取代基预测相差较远的问题,而水化能、极化率在QSAR研究中也比较少见。利用上述模型对雌、雄小鼠急性毒性进行了预测,结果表明该模型能很好地预测化合物对小鼠急性毒性,预测值与试验值误差小。

QSAR Study of 1-substitute-2-amido- benzimidazole

The configuration and quantum chemistry parameters of 8 1- substitute -2-amido-benzimidazole such as EHOMO, ELUMO, polarizability(P), hydration energy (HE), heat of formation(HF) , electrostatic potential(EP) and molar refractivity(MR) were calculated using quantum chemistry program. Quantitative structure-activity relationships (QSARs) were developed for the urgent toxicity (LD50) of male and female rat. The models made up of 4 variables had higher precision (male: r2 =0.959; female: r2 = 0.932) than that made up of 3 variables (male: r2=0.867; female: r2=0.839), suggesting that logP, ELUMO, P and HE had a good correlativity and the 4 variables affected the urgent toxicities together. These models settled the problem of the low relativity of benzene substitute compounds, and few studies on P and HE in QSARs were done formerly. In the models, ELUMO illuminated that these compounds may be the electron acceptor when they interacted with organism and HE and logP emerged at the same time, which was opposite to the normal idea that the simultaneous appearance of HE and logP should result in the not credible calculation of LD50 values. These compounds were presumed basically unreactive and the narcosis process was primary in their toxicity mechanisms. The values of toxicity depended on the degree of transfer from water phase to bio-phase and the capability of reaction with target of organism. These models had a good predictive capability, with small differences between predicted and observed values.