The molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) of 20 monoamidine compounds synthesized were studied according to their rice KARI inhibitory (in vitro) and herbicidal (in vivo) activity. For the former, an AutoDock3.0 method was used. It was found that the trend of activity change of compounds is accordant with the results from AutoDock calculations. The binding pattern of compound 9 with KARI active residues was also analyzed, and the result shows that several residues (Glu319, Asp315, Glu496, Gly253, Met254, Cys517, etc.) have very important effect on hydrogen bond, electrostatic and hydrophobic interactions. For the latter, the comparative molecular field analysis (CoMFA) was adopted. The result shows that the contributions of steric and electrostatic fields to the activity are 67.8% and 32.2% respectively. The cross-validated r_cv² and the relation coefficient r² for the model established are 0.774 and 0.999 respectively, with the F value of 1593.134 and the standard deviation (s) of 0.036. The result indicates that the 3D-QSAR model is significant and has good predictability. The research results provided useful guidance for designing more potent KARI inhibitors prior to their synthesis.

Key words: KARI, molecular docking, three-dimensional quantitative structure-activity relationship