Synthesis, Herbicidal Activity Evaluation, and Molecular Docking of Novel Acylthioureas as AHAS Inhibitors

Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) is a core enzymatic target in agrochemical research for herbicide development and has been widely investigated in recent decades. To develop novel AHAS-targeted herbicides, twenty-three acylthiourea derivatives were synthesized via fragment recombination and bioisosteric replacement strategies in this work. All target compounds were fully characterized by elemental analysis, mass spectrometry, FTIR spectroscopy, and ¹H NMR spectroscopy. Dose-response trends from the Petri dish assay at 1, 10, and 100 mg L^-1 show that root-growth inhibition increased synchronously with concentration. Preliminary bioassays across gradient concentrations (1, 10, 100 mg L^-1) revealed dose-dependent growth-inhibitory effects of several derivatives against the monocot weed Digitaria adscendens and dicot weed Amaranthus retroflexus. At 100 mg/L pre-emergence treatment, compounds 4v (76.48 ± 1.47%), 4m (69.34 ± 1.62%), and 4l (67.77 ± 1.87%) exhibited the strongest inhibitory activity, comparable to or exceeding bensulfuron-methyl (70.41 ± 1.21%). All synthesized acylthiourea derivatives exhibited less than 20% growth inhibition toward wheat and soybean, demonstrating acceptable crop selectivity. In vivo enzymatic assays at 100 mg L^-1 showed that 4l, 4m, and 4v achieved AHAS inhibition rates of 38.25 ± 1.81%, 35.74 ± 1.35%, and 38.75 ± 1.93%, comparable to or marginally exceeding that of bensulfuron-methyl (35.64 ± 1.40%). Molecular docking simulations yielded binding energies of -6.67 kcal mol^-1 (4l), -6.29 kcal mol^-1 (4m), and -6.90 kcal mol^-1 (4v), all more favorable than -5.86 kcal mol^-1 calculated for bensulfuron-methyl, indicating stronger target-enzyme binding affinity for these three compounds. This research suggests that these acylthiourea derivatives may serve as preliminary lead scaffolds for developing novel AHAS inhibitors via subsequent structural derivatization, pending further dose-response, mechanistic, and field-efficacy validation.