New library of pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives: Synthesis, herbicidal activity, and molecular docking study

Abstract

The development of nitrogen-containing heterocyclic compounds with novel structure and remarkable biological activity is always in demand. Herein, new library of pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives (1–98) was designed, synthesized, and characterized by Fourier Transform Infrared Spectoscopy (FT-IR), nuclear magnetic resonance (1H NMR), carbon-13 nuclear magnetic resonance (13C NMR), high-resolution mass spectroscopy (HRMS), and X-ray single-crystal diffraction. Their herbicidal activities were screened for the first time by Petri dish assay and pot experiment in a glasshouse. The results indicated that some of title compounds (e.g.,1, 4, 5, and 7–11) exhibited 100 % inhibition rate against the roots and stalks of Cucumis sativus, Raphanus sativus, Sorghum bicolor and Echinochloa crusgalli at a dosage of 100 mg/L, higher than the positive control Flumetsulam, a well-known commercial acetolactate synthase (ALS) inhibiting herbicide. 2-((2,4-Dichlorophenoxy)methyl)-10-(methylthio)-8-(pentylthio)-5-propyl-5,6-dihydropyri- mido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine 7 showed notable postemergence herbicidal activity against Abutilon theophrasti, Amaranthus spinosus, Chenopodium album, Digitaria sanguinalis, Echinochloa crusgalli, and Setaria viridis at a rate of 375 g/ha, and its activities were similar to the positive control Flumetsulam. Enzymatic bioassays revealed that 7, 8, and 40 displayed good inhibitory potency against ALS with 39.6 %, 39.1 %, and 40.9 % inhibition rate, respectively, comparable to that of Flumetsulam (43.5 % inhibition rate). Moreover, molecular docking analysis was conducted by using ALS protein and target ligand molecule 7. The results of molecular docking were consistent with the bioassay experiments, showing compound 7 with a new structure and excellent herbicidal potency was potent inhibitors of ALS.