Pest management science · 2026
Design, synthesis, nematicidal activity, and preliminary mechanism of pyrimidine derivatives through the scaffold hopping strategy.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Ошибки и ограничения
История · было → стало
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Du Tingting, Zhang Yan, Lu Siyu, Yang Qiuxia, Chen Jixiang
Аннотация
BACKGROUND: Plant-parasitic nematodes pose a severe threat to crops, causing over $175 billion in economic losses to global agriculture.
RESULTS: To discover novel nematicides, a database of more than 2000 molecules was constructed, and several active scaffold structures were obtained through rapid in vitro nematicidal activity screening. Eight pyrimidine derivatives containing 1,2,4-oxadiazole moieties were designed and synthesized using scaffold hopping strategies that grafted tioxazafen onto the active pyrimidine structure. Among the 38 pyrimidine compounds screened or synthesized, the majority exhibited excellent nematicidal activity. For example, compound D27 showed median lethal concentration (LC50) values of 3.7 mg/L and 11.4 mg/L against Meloidogyne incognita and Aphelenchoides besseyi, respectively, significantly superior to the lead nematicide tioxazafen. Compound D27 exhibited excellent in vivo nematocidal activity against M. incognita in tomatoes (93.3%) at 50 mg/L, which was significantly superior to the positive control tioxazafen (45.3%). Compound D27 not only induced significant oxidative stress adverse reactions in nematodes, but also decreased the frequency of head swinging and inhibited their egg-hatching capacity. In addition, compound D3 significantly inhibits the feeding and reproductive capacity of Bursaphelenchus xylophilus, affects the activity of defense enzymes (superoxide dismutase, peroxidase, and catalase) within the organism, and inhibits the activity of the succinate dehydrogenase enzyme.
CONCLUSION: This scaffold can serve as the core structure for discovery of novel nematicides. We continue to optimize this scaffold structure, aiming to discover highly effective novel nematicides in future research. © 2026 Society of Chemical Industry.
RESULTS: To discover novel nematicides, a database of more than 2000 molecules was constructed, and several active scaffold structures were obtained through rapid in vitro nematicidal activity screening. Eight pyrimidine derivatives containing 1,2,4-oxadiazole moieties were designed and synthesized using scaffold hopping strategies that grafted tioxazafen onto the active pyrimidine structure. Among the 38 pyrimidine compounds screened or synthesized, the majority exhibited excellent nematicidal activity. For example, compound D27 showed median lethal concentration (LC50) values of 3.7 mg/L and 11.4 mg/L against Meloidogyne incognita and Aphelenchoides besseyi, respectively, significantly superior to the lead nematicide tioxazafen. Compound D27 exhibited excellent in vivo nematocidal activity against M. incognita in tomatoes (93.3%) at 50 mg/L, which was significantly superior to the positive control tioxazafen (45.3%). Compound D27 not only induced significant oxidative stress adverse reactions in nematodes, but also decreased the frequency of head swinging and inhibited their egg-hatching capacity. In addition, compound D3 significantly inhibits the feeding and reproductive capacity of Bursaphelenchus xylophilus, affects the activity of defense enzymes (superoxide dismutase, peroxidase, and catalase) within the organism, and inhibits the activity of the succinate dehydrogenase enzyme.
CONCLUSION: This scaffold can serve as the core structure for discovery of novel nematicides. We continue to optimize this scaffold structure, aiming to discover highly effective novel nematicides in future research. © 2026 Society of Chemical Industry.