The linker length of glucose–fipronil conjugates has a major effect on the rate of bioactivation by β‐glucosidase

Wen, Yingjie; Jiang, Xunyuan; Yang, Chen; Meng, Huayue; Wang, Binfeng; Wu, Hongya; Zhang, Zhixiang; Han-hong, XU

doi:10.1002/ps.5170

Cited by 8 publications

(15 citation statements)

References 45 publications

(49 reference statements)

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“…In addition, endogenous ß‐glucosidases were involved in the hydrolysis of a glucose‐fipronil conjugate with an O ‐glycosidic bond, which can achieve the enzymatic release of the active aglycone . The enzymatic deglycolysation in vitro can be modulated by adjusting the linker length of the conjugate, and the in vivo insecticidal bioassay supports that the active aglycones are released from the conjugates after root absorption and exhibit the same level of activity as fipronil . Several attempts mentioned above suggest that the carrier‐mediated propesticide approach of conjugation with a nutrient moiety is a feasible approach to confer systemic properties to non‐mobile agrochemicals.…”

Section: Carrier‐mediated Propesticide Strategies For Improving Agrocmentioning

confidence: 99%

Vectorizing agrochemicals: enhancing bioavailability via carrier‐mediated transport

Marivingt-Mounir

et al. 2019

Pest Management Science

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Systemicity of agrochemicals is an advantageous property for controlling phloem sucking insects, as well as pathogens and pests not accessible to contact products. After the penetration of the cuticle, the plasma membrane constitutes the main barrier to the entry of an agrochemical into the sap flow. The current strategy for developing systemic agrochemicals is to optimize the physicochemical properties of the molecules so that they can cross the plasma membrane by simple diffusion or ion trapping mechanisms. The main problem with current systemic compounds is that they move everywhere within the plant, and this non‐controlled mobility results in the contamination of the plant parts consumed by vertebrates and pollinators. To achieve the site‐targeted distribution of agrochemicals, a carrier‐mediated propesticide strategy is proposed in this review. After conjugating a non‐systemic agrochemical with a nutrient (α‐amino acids or sugars), the resulting conjugate may be actively transported across the plasma membrane by nutrient‐specific carriers. By applying this strategy, non‐systemic active ingredients are expected to be delivered into the target organs of young plants, thus avoiding or minimizing subsequent undesirable redistribution. The development of this innovative strategy presents many challenges, but opens up a wide range of exciting possibilities. © 2018 Society of Chemical Industry

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Section: Carrier‐mediated Propesticide Strategies For Improving Agrocmentioning

confidence: 99%

Vectorizing agrochemicals: enhancing bioavailability via carrier‐mediated transport

Marivingt-Mounir

et al. 2019

Pest Management Science

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“…20 A titration curve based on authentic pNP was prepared over the range of 0.005-0.5 mM. The hydrolysis rate was calculated as: 18 Kinetic parameters were determined under optimal conditions, and the enzyme quantity was adjusted to convert less than 5% of the substrate into product. Substrate concentrations varied from 0.01 to 8 mM.…”

Section: Hydrolysis Kinetics Of the Enzymementioning

confidence: 99%

“…Insecticidal activities against P. xylostella were evaluated using a previously described leaf-dipping bioassay with some modifications. 18 All compounds were dissolved in dimethyl sulfoxide and diluted with distilled water containing Tween 80 to obtain 1.25, 0.63, and 0.31 mg L −1 for the bioassays. Brassica chinensis leaves were dipped in each test solution for 10 s. Mortalities were determined 24 h after treatment.…”

Section: Insects and Bioassaysmentioning

confidence: 99%

“…A later study was conducted to optimize the length of the linker structure in GOF, leading to new glucose-O-fipronil conjugates that produce hydrolysates with insecticidal activity comparable with that of fipronil. 18 However, the optimized conjugates suffer from relatively low hydrolytic rates due to ⊎-glucosidase (less than 60% hydrolyzed over 30 min), which impedes their effectiveness in vivo. Therefore, it is necessary to further improve the hydrolysis rate of glucose-O-fipronil conjugates, thereby enhancing their utilization efficiency to meet the need for practical application.…”

Section: Introductionmentioning

confidence: 99%

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Design of new glycosyl–O‐fipronil conjugates with improved hydrolysis efficiency assisted by molecular simulations

Wang¹,

Yang²,

Jiang

et al. 2022

Pest Management Science

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BACKGROUND: In a previous study, we showed that two glycosyl-pesticide conjugates with a ⊎-D-glucoside moiety, N-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl)-sulfinyl]-1H-pyrazol-5-yl}-2-aminoethyl-⊎-D-glucopyranoside (GOF) and N-{3-cyano-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfinyl]-1H-pyrazol-5-yl}-1-(2-triazolethyl-⊎-D-glucopyranoside)-1H-1,2,3-triazole-4-methanamine (GOTF), can move in the phloem and be hydrolyzed by ⊎-glucosidase at different rates. Simulations were carried out to investigate differences in the hydrolysis process in GOF, GOTF and p-nitrophenyl ⊎-D-glucopyranoside (pNPG). A new series of glycosyl-O-fipronil conjugates was then designed and synthesized based on the simulation results. The phloem mobilities of the new conjugates were examined using a Ricinus model, and their hydrolysis efficiencies based on ⊎-glucosidase were determined.RESULTS: New glycosyl-O-fipronil conjugates GOE2-6 were designed and synthesized. To reduce steric hindrance, the conjugating site of the glycone moiety was moved to the 4 0 -sulfonyl group on the pyrrole ring. As a result, the hydrolysis efficiencies of the new conjugates were significantly improved, with GOE4 having the highest hydrolysis efficiency. All five conjugates could be transported in Ricinus phloem sap, consistent with previously studied glycosyl-O-fipronil conjugates. The insecticidal activities of the conjugates were tested against Plutella xylostella.CONCLUSION: A strategy for the development of new phloem-mobile pesticides was proposed: linking a glycosyl group to the existing pesticide structure with a linear alkyl connection approximately four carbons in length. The resultant conjugates feature not only good phloem mobility, but also potential high bioactivity due to the efficient release of active pesticide components under the action of glucosidase.

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“…However, the structure–activity relationship of tralopyril conjugates has not yet been investigated, especially for the linker structure. In previous studies, the linker structure between the nutrient promoiety and active ingredient influence the bioactivity and phloem mobility of the conjugates [ 8 , 17 ]. Hence, the aim of the present study is to elucidate the structure–activity relationship for the linker between amino acid promoiety and tralopyril.…”

Section: Introductionmentioning

confidence: 99%

Vectorizing Pro-Insecticide: Influence of Linker Length on Insecticidal Activity and Phloem Mobility of New Tralopyril Derivatives

Chen

Liu

et al. 2021

Molecules

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To improve the proinsecticidal activity and phloem mobility of amino acid–tralopyril conjugates further, nine conjugates were designed and synthesized by introducing glutamic acid to tralopyril, and the length of the linker between glutamic acid and tralopyril ranged from 2 atoms to 10 atoms. The results of insecticidal activity against the third-instar larvae of P. xylostella showed that conjugates 42, 43, 44, and 45 (straight-chain containing 2–5 atoms) exhibited good insecticidal activity, and their LC50 values were 0.2397 ± 0.0366, 0.4413 ± 0.0647, 0.4400 ± 0.0624, and 0.4602 ± 0.0655 mM, respectively. The concentrations of conjugates 43–45 were higher than that of conjugate 42 in the phloem sap at 2 h, and conjugate 43 showed the highest concentration. The introduction of glutamic acid can improve phloem mobility. The in vivo metabolism of conjugates 42 and 43 was investigated in P. xylostella, and the parent compound tralopyril was detected at concentrations of 0.5950 and 0.3172 nmol/kg, respectively. According to the above results, conjugates 42 and 43 were potential phloem mobile pro-insecticide candidates.

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The linker length of glucose–fipronil conjugates has a major effect on the rate of bioactivation by β‐glucosidase

Abstract: This study provides a potential strategy to optimize the substrate structure to enhance hydrolytic specificity in order to design appropriate phloem mobile pro-pesticides. © 2018 Society of Chemical Industry.

Cited by 8 publications

References 45 publications

Vectorizing agrochemicals: enhancing bioavailability via carrier‐mediated transport

Vectorizing agrochemicals: enhancing bioavailability via carrier‐mediated transport

Design of new glycosyl–O‐fipronil conjugates with improved hydrolysis efficiency assisted by molecular simulations

Vectorizing Pro-Insecticide: Influence of Linker Length on Insecticidal Activity and Phloem Mobility of New Tralopyril Derivatives

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