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目的应用三维定量构效关系(3D-QSAR)研究噻唑类衍生物结构的二氢乳清酸脱氢酶抑制活性,为该类药物的设计和筛选提供可靠的理论依据。方法针对38个以噻唑为基本骨架的二氢乳清酸脱氢酶抑制剂,分别应用分子力场分析(Co MFA)和比较分子相似性指数分析(Co MSIA)2种经典的方法进行了三维定量构效关系(3D-QSAR)研究,建立相关模型,验证模型的预测能力,三维等势图分析噻唑类衍生物结构与活性的关系。结果 Co MFA模型的交叉验证系数q2为0.796,相关系数r2为0.978;Co MSIA模型的q2以及r2分别为0.721和0.976;2种模型对化合物的活性预测与实际值接近;三维等势图可以全面直观的分析化合物结构对其活性的影响。结论该3D-QSAR模型三维等势图揭示了结构特征与抑制活性的关系,模型具有较好的预测能力和较强的稳定性,为进一步开发研究打下了较好的基础。
OBJECTIVE: To study the inhibitory activity of dihydro-orotate dehydrogenase of thiazole derivatives by 3D-QSAR and to provide a reliable theoretical basis for the design and screening of these drugs. Methods Thirty-eight dihydro-orotate dehydrogenase inhibitors with thiazole as the basic skeleton were applied in two-dimensional (2D) methods, CoMFA and Co MSIA respectively. Quantitative structure-activity relationship (3D-QSAR) study, the establishment of relevant models to verify the predictive ability of the model, three-dimensional isometry analysis of the relationship between the structure and activity of thiazole derivatives. Results The cross-validation coefficient q2 of Co MFA model was 0.796, the correlation coefficient r2 was 0.978. The q2 and r2 of Co MSIA model were 0.721 and 0.976, respectively. The activity prediction of the two compounds was close to the actual value. The three- Intuitive analysis of the compound structure on its activity. Conclusion The 3D isostrogram of 3D-QSAR model reveals the relationship between structural features and inhibitory activity. The model has good predictive ability and strong stability, laying a good foundation for further development.