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采用比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA),系统地研究了40个苯并呋喃类N-肉豆蔻酰基转移酶(NMT)抑制剂的三维定量构效关系.在CoMFA研究中,考察了网格点步长对模型统计结果的影响.在CoMSIA研究中,研究了各种分子场组合、网格点步长和衰减因子对模型统计结果的影响,发现立体场、静电场、疏水场和氢键受体场的组合可得到最佳模型.所建立的CoMFA和CoMSIA模型的交叉相关系数q2值分别为0.759和0.730,均具有较强的预测能力.利用CoMFA和CoMSIA模型的三维等值线图直观地解释了化合物的构效关系,阐明了化合物结构中苯并呋喃环上各位置取代基对抑酶活性的影响,为进一步结构优化提供了重要依据.
Three-dimensional QSARs of 40 benzofuran N-myristoyltransferase (NMT) inhibitors were systematically investigated using comparative molecular force field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) In the CoMFA study, the effect of the lattice point step size on the statistical results of the model was investigated.In the CoMSIA study, the effects of various molecular field combinations, lattice point steps and attenuation factors on the statistical results of the model were investigated, The optimal model was obtained by the combination of field, electrostatic field, hydrophobic field and hydrogen bond acceptor field.The cross-correlation coefficient q2 values of CoMFA and CoMSIA models established were 0.759 and 0.730, respectively, with strong predictive ability.The CoMFA And the three-dimensional contour map of the CoMSIA model intuitively explained the structure-activity relationship of the compounds, and elucidated the influence of substituents on the benzofuran ring at various positions on the inhibitory enzyme activity, which provided an important basis for further structural optimization.