Abstract

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) represents a potential target for novel herbicide development. To discover the more promising HPPD inhibitor, we designed and synthesized a series of bis-5-cyclopropylisoxazole-4-carboxamides with different linkers using a multitarget pesticide design strategy. Among them, compoundsb9andb10displayed excellent herbicidal activities versusDigitaria sanguinalis(DS) andAmaranthus retroflexus(AR) with the inhibition of about 90% at the concentration of 100 mg/L in vitro, which was better than that of isoxaflutole (IFT). Furthermore, compoundsb9andb10displayed the best inhibitory effect versusDSandARwith the inhibition of about 90 and 85% at 90 g (ai)/ha in the greenhouse, respectively. The structure–activity relationship study showed that the flexible linker (6 carbon atoms) is responsible for increasing their herbicidal activity. The molecular docking analyses showed that compoundsb9andb10could more closely bind to the active site of HPPD and thus exhibited a better inhibitory effect. Altogether, these results indicated that compoundsb9andb10could be used as potential herbicide candidates targeting HPPD.

Journal of Agricultural and Food Chemistry, IF=5.895

https://pubs.acs.org/doi/10.1021/acs.jafc.2c08912