Mechanism of metamifop inhibition of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in Echinochloa crus-galli.

Acetyl-coenzyme A carboxylase (ACCase) plays crucial roles in fatty acid metabolism and is an attractive target for herbicide discovery. Metamifop is a novel ACCase-inhibiting herbicide that can be applied to control sensitive weeds in paddy fields. In this study, the effects of metamifop on the chloroplasts, ACCase activity and carboxyltransferase (CT) domain gene expression in Echinochloa crus-galli were investigated. The results showed that metamifop interacted with the CT domain of ACCase in E. crus-galli. The three-dimensional structure of the CT domain of E. crus-galli ACCase in complex with metamifop was examined by homology modelling, molecular docking and molecular dynamics (MD) simulations. Metamifop has a different mechanism of inhibiting the CT domain compared with other ACCase inhibitors as it interacted with a different region in the active site of the CT domain. The protonation of nitrogen in the oxazole ring of metamifop plays a crucial role in the interaction between metamifop and the CT domain. The binding mode of metamifop provides a foundation for elucidating the molecular mechanism of target resistance and cross-resistance among ACCase herbicides, and for designing and optimizing ACCase inhibitors.

Design, synthesis and herbicidal evaluation of novel 4-(1H-pyrazol-1-yl)pyrimidine derivatives.

BACKGROUND: A series of novel pyrazolylpyrimidine derivatives were designed, synthesised and characterised by IR, (1) H NMR, (13) C NMR, mass spectroscopy and elemental analysis. The herbicidal activities of 30 pyrazolylpyrimidine derivatives were assessed. RESULTS: Nine compounds caused good herbicidal activity for Pennisetum alopecuroides L. Among them, N-ethyl-6-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-pyrimidin-4-amine exhibited the strongest inhibitory activity against the root growth of P. alopecuroides, with an IC50 of 1.90 mg L(-1) . 2-Methyl-4-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-6-(prop-2-yn-1-yloxy)pyrimidine produced the highest inhibition of chlorophyll level in seedlings of P. alopecuroides (IC50 = 3.14 mg L(-1) ). CONCLUSION: The structure-activity relationship indicated that the alkynyloxy group at the 6-position on the pyrimidine ring played a very important role for bleaching activities. When the alkynyloxy group was replaced by alkoxy, amino, alkylthio and alkylsulfonyl groups, the bleaching activities of the compounds were diminished. However, the compounds substituted by an amino at the 6-position of the pyrimidine ring exhibited excellent inhibition activities against weed root growth.

Design, synthesis and herbicidal activities of novel 4-(1H-pyrazol-1-yl)-6-(alkynyloxy)-pyrimidine derivatives as potential pigment biosynthesis inhibitors.

BACKGROUND: With the objective of finding novel valuable herbicidal candidates, a series of novel 4-(1H-pyrazol-1-yl)-6-(alkynyloxy)-pyrimidine derivatives were synthesised and their herbicide activities were evaluated in vivo. RESULTS: The results showed that many target compounds expressed bleaching activities. Among these, compound 5 h showed the best bleaching activity to gramineous weeds, being able to produce the highest inhibition of chlorophyll level in seedlings of Pennisetum alopecuroides L. (IC50 = 3.48 mg L(-1) ). Moreover, compound 5 h expressed good selective toxicity between gramineous P. alopecuroides L. and broadleaf plant Brassica campestris L. CONCLUSIONS: The present work demonstrates that pyrimidine derivatives containing pyrazole can be used as potential lead compounds for developing novel pigment biosynthesis inhibitors.