Design, synthesis and herbicidal evaluation of novel ester-functionalized N-phenylphthalimide derivatives containing...

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) represents a crucial target for the development of highly effective and environmentally sustainable herbicides. Present N-phenylphthalimide PPO inhibitors often have limited herbicidal spectra and inadequate crop selectivity. Consequently, we concurrently incorporated pyridine and ester functional groups into the N-phenylphthalimide framework to create innovative, highly efficient broad-spectrum herbicide candidate compounds.

Based on active scaffold splicing strategy, a number of structurally innovative N-phenylphthalimide derivatives were designed, synthesized and characterized. Glasshouse herbicidal activity assays indicated that compound II-f13 effectively suppressed six target weed species. At 300 g ai ha^-1, compound II-f13 demonstrated broad-spectrum herbicidal efficacy. Meanwhile, compound II-f13 exhibited greater crop safety compared to flumiclorac-pentyl for Glycine max, Gossypium hirsutum and Triticum aestivum within the 75-300 g ai ha^-1 dosage range. In vitro enzyme activity assays confirmed that the target compound is a typical PPO inhibitor. Moreover, molecular docking, molecular dynamics (MD),and density functional theory (DFT) calculations indicated that compound II-f13 establishes strong hydrogen bonds with ASN-468 of Nicotiana tabacum PPO (NtPPO), while also demonstrating remarkable chemical reactivity, electrostatic fields and elevated polarity.

Our research indicates that the novel N-phenylphthalimide derivative II-f13, which features a pyridine moiety and an ester group, is an excellent option for the discovery of new PPO inhibitor herbicide. © 2026 Society of Chemical Industry.