JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Xin Wu,Zili Yang,Chunlin Song,Mengwei Bu,Weiguo Li,Jiang Duan,Guang-Fu Yang,Aidong Zhang
Fosmidomycin (FOS) is a natural product inhibiting the DXR enzyme in the MEP pathway and has stimulated interest for finding more suitable FOS analogues. Herein, two series of FOS analogue hydroxamate-containing bisphosphonates as proherbicides were designed, with bisphosphonate replacing the phosphonic unit in FOS while retaining the hydroxamate (BPF series) or replacing it with retro-hydroxamate (BPRF series). The BPF series were synthesized through a three-step reaction sequence including Michael addition of vinylidenebisphosphonate, N-acylation, and deprotection, and the BPRF series were synthesized with a retro-Claisen condensation incorporated into the reaction sequence. Evaluation on model plants demonstrated several compounds having considerable herbicidal activities, and in particular, compound 8m exhibited multifold activity enhancement as compared to the control FOS. The proherbicide properties were comparatively validated. Furthermore, DXR enzyme assay, dimethylallyl pyrophosphate rescue, and molecular docking verified 8m to be a promising proherbicide candidate targeting the DXR enzyme. In addition, 8m also displayed good antimalarial activities.
研究领域:
植物学
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药理学
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农业科学
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高影响因子
BIOLOGIA PLANTARUM
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2011
·Vol. 55
·期 4
·669-674
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IF 1.582
Zeng Q. -P.,Zeng X. -M.,Yang R. -Y.,Yang X. -Q.
Although crosstalk between cytosolic and plastidic terpenoid pathways has been validated in many plant species, we report here for the first time a striking elevation of the nucleus-encoded artemisinin biosynthesis relevant DBR2 mRNA following the incubation of plants with fosmidomycin (FM). FM decreased singlet oxygen ( 1 O 2 ) scavengers such as β-carotene and α-tocopherol and subsequently invoked 1 O 2 burst. The treatment of plants with fluridone (FD) neither decreased α-tocopherol content nor triggered 1 O 2 emission. In conclusion, FM can up-regulate 1 O 2 -sensitive nuclear genes responsible for artemisinin biogenesis by mitigating the accumulation of plastidic scavenging terpenoids, thereby eliciting 1 O 2 generation and initiating 1 O 2 retrograde signaling.
研究领域:
植物生物化学
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分子遗传学
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植物化学
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PEST MANAGEMENT SCIENCE
·
2026
·
IF 4.2
Zili Yang,Liru Zheng,Qinping Hu,Mengwei Bu,Jiang Duan,Weiguo Li,Aidong Zhang
BACKGROUND The rapid evolution and spread of herbicide resistance poses a great challenge to the sustainability of modern agriculture and finding new herbicides based on novel modes of action (MOA) has become an urgent need. The enzyme 1-deoxy- d -xylulose-5-phosphate reductoisomerase (DXR) in the 2- C -methyl- d -erythritol 4-phosphate (MEP) pathway is considered an ideal novel target for developing new herbicides and therefore its natural inhibitor fosmidomycin (FOS) is an excellent starting point from which to design new herbicidal candidates. RESULTS This work presents the design and synthesis of a series of β -substituted FOS analogs 10a – m and 11a – m and a prodrug 15i , the diethyl ester of 11i , for evaluating their herbicidal activity. Most compounds exhibited high inhibition activity toward the DXR enzyme in the MEP pathway, and 11i and 11l were among the most active, with half-maximal inhibitory concentrations of 0.24 and 0.27 μ m , respectively. In pre- and post-emergence tests on model plants, ten compounds had higher activities than FOS, and 15i achieved more than tenfold pre-emergence and twofold post-emergence activity against the test weeds. The MEP pathway rescue of Arabidopsis inhibited by 11i as a representative had a higher rescue rate than that by FOS, while molecular docking revealed binding enhancement in the DXR active site due to β -substitution, suggesting that β -substituted FOS analogs may be herbicidally active by targeting DXR, like the MOA of FOS. CONCLUSION The combination of β -substitution with prodrug derivation to modify the lead structure FOS is an effective strategy for developing herbicide-active FOS analogs. © 2026 Society of Chemical Industry.
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高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2025
·
IF 4
Zili Yang,Xin Chen,Liru Zheng,Qinping Hu,Mengwei Bu,Jiang Duan,Aidong Zhang
Inhibitor design based on the natural product fosmidomycin (FOS) as a lead structure is a promising strategy in search of herbicidally active compounds that may target the DXR enzyme in the MEP pathway. Herein, two metal ion chelating groups, aminol and amide, were used to replace the hydroxamate moiety of FOS, and two types of non-hydroxamate FOS analogs, namely aminol- ( 5a ∼ n and 6a ∼ o ) and phenylamide-containing ( 10a ∼ v ) phosphonic acids were designed and synthesized by establishing facile routes involving the Michaelis-Arbuzov reaction, epoxide ring-opening, acrylamidation, Michael addition, and phosphonate hydrolysis. In the pre-emergency bioactivity screening several compounds demonstrated herbicidal activities superior to FOS, including 5c , 5 h , 10a , 10d , 10e , etc. In particular, 10e showed an 18.7-fold inhibition activity against Arabidopsis thaliana and 16.1- and 10.8-fold activities against the root and stalk of Echinochloa crus-galli , respectively, in comparison with that of FOS. In the post-emergency assay, 10e also displayed 1.9- and 2.1-fold inhibition activities against E. crus-galli and Amaranthus retroflexus . Enzyme inhibition assay revealed the inhibition activities of some compounds to the DXR enzyme far below that of FOS, while the plant growth rescue failed from the inhibition by 5c and 10e by adding dimethylallyl pyrophosphate (DMAPP), a downstream product of the MEP pathway, both suggesting that some targets instead of the DXR enzyme might be involved in the inhibition by the active compounds. Nevertheless, this work demonstrated that using bioisosteric replacement based on the lead structure FOS is an effective strategy for developing highly herbicidal active compounds.
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