No abstract

Phytoene desaturase (PDS) is not only an important enzyme in the biosynthesis of carotenoids but also a promising target for herbicide discovery. However, in recent years, no expected PDS inhibitors with new scaffolds have been reported. Hence, a solution for developing PDS inhibitors is to search for new compounds with novel chemotypes based on the PDS protein structure. In this work, we integrated structure-based virtual screening, structure-guided optimization, and biological evaluation to discover some PDS inhibitors with novel chemotypes. It is noteworthy that the highly potent compound 1b, 1-(4-chlorophenyl)-2-((5-(hydroxymethyl)-4-(3-(trifluoromethyl)­phenyl)-4H-1,2,4-triazol-3-yl)­thio)­ethan-1-one, exhibited a broader spectrum of post-emergence herbicidal activity at 375–750 g/ha against six kinds of weeds than the commercial PDS inhibitor diflufenican. Surface plasmon resonance (SPR) assay showed that the affinity of our compound 1b (K D = 65.9 μM) to PDS is slightly weaker but at the same level as diflufenican (K D = 38.3 μM). Meanwhile, determination of the phytoene content and PDS mRNA quantification suggested that 1b could induce PDS mRNA reduction and phytoene accumulation. Moreover, 1b also caused the increase of reactive oxygen species (ROS) and the change of ROS-associated enzyme activity in albino leaves. Hence, all these results indicated the feasibility of PDS protein structure-based virtual screen and structure optimization to search for highly potent PDS inhibitors with novel chemotypes for weed control.

A series of novel 3-phenoxy-4-(3-trifluoromethylphenyl)pyridazines 2–5 were designed, based on the structure of our previous lead compound 1 through the in silico structure-guided optimization approach. The results showed that some of these new compounds showed a good herbicidal activity at the rate of 750 g ai/ha by both pre- and post-emergence applications, especially compound 2a, which displayed a comparable pre-emergence herbicidal activity to diflufenican at 300–750 g ai/ha, and a higher post-emergence herbicidal activity than diflufenican at the rates of 300–750 g ai/ha. Additionally, 2a was safe to wheat by both pre- and post-emergence applications at 300 g ai/ha, showing the compound’s potential for weed control in wheat fields. Our molecular simulation studies revealed the important factors involved in the interaction between 2a and Synechococcus PDS. This work provided a lead compound for weed control in wheat fields.

Chemical investigation on the stem and root of Melicope pteleifolia afforded three new prenylated benzene metabolites as racemic mixtures, named pteleifolins A–C (1–3, resp.). Their gross structures were elucidated on the basis of spectroscopic analysis, especially 2D‐NMR experiments. An enantiomer resolution of (±)‐1 using chiral HPLC was performed, and the absolute configuration of the enantiomers were determined to be (+)‐(S)‐1 and (−)‐(R)‐1 by means of circular‐dichroism analysis.