The application of herbicides plays a critical role in ensuring food security. However, the long-term overuse of herbicides can lead to a range of adverse effects. Therefore, it is essential to develop innovative and sustainable herbicides. A series of pyridazinone derivatives targeting phytoene desaturase (PDS) were designed and synthesized by using a structure-based drug design strategy. A bioassay showed that 16c (100%, 85%) exhibited stronger herbicidal activity against portulaca oleracea (P.o.) than that of norflurazon (NRF, 60%, 45%) in both post- and pre-emergence applications at a dosage of 150 g a.i./ha, while also showing greater safety to nontarget organisms. Meanwhile, levels of 15-cis-phytoene, carotenoids, and chlorophyll revealed that 16c effectively inhibited PDS activity. Molecular dynamics simulations and binding action assays confirmed that Arg195 is a key residue for the interaction between 16c and Synechococcus PDS (SynPDS). Therefore, 16c could be developed as a potent PDS inhibitor for herbicides.
Chao Chen, Yan Li, Wei Zhang et al.· Journal of Agricultural and...· 0 citations
The use of herbicides represents one of the effective weed management strategies. To create high-efficiency, low-risk protoporphyrinogen IX oxidase (PPO)-targeted herbicides, a set of novel N-phenylphthalimides bearing 1,3,4-oxadiazole and acylhydrazide fragments was designed and synthesized. Bioassays revealed that most of the compounds possessed potent herbicidal activity against six common weeds. Compound A9 exerted good inhibitory effects on Nicotiana tabacum PPO (NtPPO) with a Ki of 14.0 nM, outperforming commercial flumioxazin (46.3 nM) and flumiclorac-pentyl (52.0 nM). Molecular docking validated that A9 binds tightly to NtPPO via hydrogen bonds with Arg98 (2.8 Å), π–π stacking with Phe392, and π–alkyl sandwich interactions with Leu356/Leu372. Assays with PPO-deficient and PPO-complemented Escherichia coli strains, alongside AtPPO-overexpressing and mutant Arabidopsis, collectively verified A9 functions as a target-specific PPO inhibitor.
Wang Geng, Yan Li, Wei Zhang et al.· Journal of Agricultural and...· 0 citations
