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

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.

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

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 Kappi 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 q2 and the relation coefficient r2 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(-lgKappi ) for ten test set compounds. These results will be useful for design and synthesis of highly active compounds.