Design and Synthesis of N-phenyl Phthalimides as Potent Protoporphyrinogen Oxidase Inhibitors

Abstract

Protoporphyrinogen oxidase (PPO) has been identified as one of the most promising targets for herbicide discovery. A series of novel phthalimide derivatives were designed by molecular docking studies targeting the crystal structure of mitochondrial PPO from tobacco (mtPPO, PDB: 1SEZ) by using Flumioxazin as a lead, after which the derivatives were synthesized and characterized, and their herbicidal activities were subsequently evaluated. The herbicidal bioassay results showed that compounds such as 3a (2-(4-bromo-2,6-difluorophenyl) isoindoline-1,3-dione), 3d (methyl 2-(4-chloro-1,3-dioxoisoindolin-2-yl)-5-fluorobenzoate), 3g (4-chloro-2-(5-methylisoxazol-3-yl) isoindoline-1,3-dione), 3j (4-chloro-2-(thiophen-2-ylmethyl) isoindoline-1,3-dione) and 3r (2-(4-bromo-2,6-difluorophenyl)-4-fluoroisoindoline-1,3-dione) had good herbicidal activities; among them, 3a showed excellent herbicidal efficacy against A. retroflexus and B. campestris via the small cup method and via pre-emergence and post-emergence spray treatments. The efficacy was comparable to that of the commercial herbicides Flumioxazin, Atrazine, and Chlortoluron. Further, the enzyme activity assay results suggest that the mode of action of compound 3a involves the inhibition of the PPO enzyme, and 3a showed better inhibitory activity against PPO than did Flumioxazin. These results indicate that our molecular design strategy contributes to the development of novel promising PPO inhibitors.

Novel [1,2,4]-Triazolo[3,4-b]-[1,3,4]thiadizoles as Potent Pyruvate Kinase Inhibitors for Fungal Control

“…The result of the Ramachandran plot is shown in Figure S1 (Supporting Information), the RsPK 3D structure simulated with the AlphaFold 2 was of high quality and reached the standard without further refinement. Binding energy is an important factor for assessing the interaction between a receptor protein and its ligands. , At a computation level, the higher the binding energy, the higher the fungicidal activity of target compounds. According to the SARs found in previous studies, we evaluated the binding energy of the designed compounds 5a – 5g with RsPK using the AutoDock Vina, and then synthesized and assessed their performance against fungi.…”

“…Binding energy is an important factor for assessing the interaction between a receptor protein and its ligands. 33,34 At a computation level, the higher the binding energy, the higher the fungicidal activity of target compounds. According to the SARs found in previous studies, 17 we evaluated the binding energy of the designed compounds 5a−5g with RsPK using the AutoDock Vina, and then synthesized and assessed their performance against fungi.…”

Design, Synthesis, and Herbicidal Activity of Thioether Containing 1,2,4-Triazole Schiff Bases as Transketolase Inhibitors

“…The postemergence herbicidal activities of the tested compounds were evaluated between 50 and 90 g [active ingredient (ai)]/ha in a greenhouse . Nine seeds of these plants ( AR and DS ) were sown at a depth of 5 mm in a mixture of vermiculite/nutrient-enriched soil (1:1, m/m) with some water at 4 cm below the surface and then cultivated at 20–25 °C.…”

“…The postemergence herbicidal activities of the tested compounds were evaluated between 50 and 90 g [active ingredient (ai)]/ha in a greenhouse. 39 Nine seeds of these plants (AR and DS) were sown at a depth of 5 mm in a mixture of vermiculite/nutrient-enriched soil (1:1, m/m) with some water at 4 cm below the surface and then cultivated at 20−25 °C. When the weeds (DS and AR) grew approximately to the two-and three-leaf stages, they were treated with the test compound solution by a walking spray tower and then cultivated for 1 week.…”

Design, synthesis and fungicidal activity of 3,4-dichloroisothiazolocoumarin-containing strobilurins

“…The structure of cytochrome bc 1 complex was obtained from RCSB PDB database (PDB code 3L70). The docking procedure was conducted according to the reported literature [25]. The structures of complexes were presented by Pymol.…”