酚类化合物麻醉毒性的CoFMA研究
CoMFA Study on Polar Narcosis Toxicity of Phenols
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摘要: 通过比较分子力场分析方法（CoMFA）建立酚类化合物对梨形四膜虫极性麻醉毒性（pT）的三维定量结构-活性相关（3D-QSAR）模型。基于训练集41个化合物建立了预测模型，10个化合物作为验证集（含模板分子）。训练集的CoMFA模型显示立体场、静电场对麻醉毒性贡献依次为53.9%和46.1%。其交叉验证相关系数（Rcv2）为0.735，非交叉验证相关系数（R2）为0.971。对训练集、测试集中的化合物麻醉毒性进行预测，显示出较强的稳定性和良好的预测能力。根据CoMFA模型的立体场和静电场三维等势线图可知，在羟基的间、对位上引入小体积基团，以及邻、对位有负电性基团，有利于提高酚类衍生物的麻醉毒性。基于此，设计了7种具有更高麻醉毒性的酚类化合物，有待生物医学实验验证。Abstract: The polar narcosis toxicity (pT) of phenols against Tetrahymena pyriformis was applied to 3D-QSAR models by using the comparative molecular field analysis (CoMFA) method. The predicting model was established based on the training set of 41 compounds, which was verified by the test set of 10 compounds (containing template molecule). The results showed that the contributions of steric and electrostatic fields were 53.9% and 46.1%, respectively. The coefficients of the cross-validation (Rcv2) and the non cross-validation (R2) were 0.735 and 0.971, respectively. The model were used to predict the activities of the compounds for the training set and the testing set. The results indicated that the model had strong stability and good predictability. According to the three-dimensional equipotential maps of the CoMFA model, it can be seen that the introduction of small-volume groups in the meta- and para-positions of hydroxyl groups, as well as ortho-and para-negative groups, is conducive to improving the anesthetic toxicity of phenolic derivatives. Based on the 3D-contour maps, seven phenols with higher polar narcosis toxicity were designed; however, those are still needed to be verified by the experimental results.
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