Quantitative prediction of AHAS inhibition by pyrimidinylsalicylate based herbicides

Acetohydroxyacid synthase (AHAS) inhibition by pyrimidylsalicylate based herbicides is studied within the framework of quantitative structure-activity relationship (QSAR) methodology. A general model for this family of herbicides is developed to predict molar pI50, i.e. the logarithm of the reciprocal molar concentration of herbicide required for 50% inhibition of the AHAS activity. The model, which involves only four descriptors: two geometric and two quantum chemical, accounting for the steric, electrostatic and hydrogen bonding interactions responsible for the binding of the herbicide to the enzyme; predicts the molar pI50 with a squared correlation coefficient of 0.89 and a standard deviation of 0.43. The training set includes 30 structures of substituted O-(4,6-dimethoxypyrimidin-2-yl) salicylic acids and thio analogs, covering a pI50 range from about 3 to 8 U. The model is validated with an external set of 13 structures not included in the training set.