拟南芥乙酰羟基酸合成酶与磺酰脲的相互作用以及CoMFA研究

Interaction and CoMFA Studies on A. thaliana Acetohydroxyacid Synthase by Sulfonylureas

在分子水平上较为详尽地研究了85个磺酰脲类化合物与植物源野生型拟南芥AHAS酶的离体相互作用,测定了这些化合物对AHAS酶的抑制常数Kiapp.采用比较分子力场方法(CoMFA)对这些化合物与AHAS酶的相互作用进行了三维构效关系研究,用此模型预测了检验组10个化合物的pKiapp值,模型的预测结果与测试结果一致.

Acetohydroxyacid synthase（AHAS） is the target for sulfonylurea, imidazolinone, triazolopymiding sulfonaniline and pyrimidin-2-yl salicylate herbicides. The interactions between wild type A. thaliana Acetohydroxyacid synthase（AHAS） and 85 synthesized sulfonylureas in vitro were studied, obtained Ki^app values of all compounds by the method of Westerfeld and Singh. The structure-activity relationship and 3D-QSAR was investigated by using comparative molecular fields analysis（CoMFA）. The cross-validated q^2 and the relation coefficient r^2 for the model established by the study are 0. 811 and 0. 934 respectively, with a F value of 246. 506 and a standard deviation（s） of 0. 419. The obtained satisfied QSAR model was is consistent with those based on in vivo data and showed a high ability to predict the biological activity（-lgKi^app） for ten test set compounds. These results will be useful for design and synthesis of highly active compounds.