2D-QSAR和HQSAR研究6-O-芳基酮内酯衍生物的定量构效关系
2D-QSAR and HQSAR study on quantitative structure-activity relationship of 6-O-aryl ketolides derivatives
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摘要: 酮内酯作为第3代大环内酯类抗生素，不仅对耐药菌有良好的活性，而且克服了诱导耐药性，成为了大环内酯类药物的研究热点。针对6-O-芳基酮内酯衍生物，本文运用二维定量构效关系(2D-QSAR)和分子全息定量构效关系(HQSAR)两种方法，以49个化合物作为训练集构建构效关系模型。所建2D-QSAR和HQSAR模型的相关系数r2分别为0.849和0.975，交叉验证系数q2分别为0.803和0.926。通过测试集验证表明所建模型均具有较好的预测能力(r2分别为0.782和0.878)。研究结果可为大环内酯类抗生素药物进一步的优化设计提供理论指导。Abstract: As the third-generation antibacterial macrolides，ketolides not only have good activity against drug-resistant strains，but also overcome the induction of resistance to drugs，and have become the focus in the investigation of the macrolides.The 2D-QSAR(2-dimensional quantitative structure-activity relationships) and HQSAR(hologram QSAR) were used to develop QSAR models with a training set of 49 6-O-aryl ketolide derivatives.Both 2D-QSAR and HQSAR models yielded good results，including high conventional correlation(r2) coefficients(0.849，0.975) and across-validated(q2) coefficients(0.803，0.926).Both of the models were validated by an external test set of 9 compounds，which gave a satisfactory predictive r2 of 0.782 and 0.878，respectively.This study might provide insights into further structural optimization of macrolides.
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Keywords:
- macrolides /
- ketolides /
- 2D-QSAR /
- HQSAR /
- quantitative structure-activity relationship(QSAR)
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