具有除草活性的大环内酯类衍生物的定量构效关系

QSAR of Macrolactone Derivatives with Herbicidal Activity

研究了一系列结构新颖的具有除草活性的大环内酯衍生物的定量构效关系(QSAR). 构建的比较分子力场分析(CoMFA)、比较分子近似指数分析(CoMSIA)和全息定量构效关系(HQSAR)分子模型的交叉验证系数 rc2v均大于 0.5, 非交叉验证系数 r2 都超过 0.8, 表明获取的 QSAR 模型具有可信的预测能力. 对 CoMFA、CoMSIA模型的三维(3D)等势图分析, 发现除了立体场和静电场外, 疏水场和氢键受体场也是影响大环内酯类化合物除草活性的重要因素. 构建的 HQSAR 模型的原子贡献图提示的结构改造信息与三维 QSAR 的结果基本一致. 利用 CoMFA、CoMSIA 模型提供的信息, 对目前已合成的活性最高化合物 B1-3 进行分子结构改造, 预测结果发现部分化合物可能具有更好的除草活性.

We studied the quantitative structure-activity relationships （QSAR） of macrolactone derivatives.Statistical results from the established comparative molecular field analysis （CoMFA）,the comparative molecular similarity indices analysis （CoMSIA）,and the hologram quantitative structure-activity relationship （HQSAR） models showed believable predictability based on the cross-validated value （rc2v0.5） and the non cross-validated value （r20.8）.A contour maps analysis of the CoMFA and CoMSIA models showed that the hydrophobic and hydrogen-bond acceptor fields are important factors that affect the herbicidal activity of macrolactone compounds except for the steric and electrostatic fields.The structural modification information from the different atom contributions in the HQSAR model is in agreement with those of the 3D-QSAR models.According to the results from the CoMFA and CoMSIA models,the structure of compound B1-3 with the best herbicidal activity was modified and some designed compounds were predicted to have higher activity.