Discovery and quantitative structure–activity relationship study of lepidopteran <scp>HMG‐CoA</scp> reductase inhibitors as selective insecticides

Zang, Yang-yang; Li, Yuan-mei; Yin, Yue; Chen, Shanshan; Kai, Zhen-peng

doi:10.1002/ps.4561

Cited by 10 publications

(13 citation statements)

References 27 publications

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“…Citronellol, HPLC-grade n-hexane and acetonitrile were purchased from Sigma-Aldrich (St. Louis, MO). The hormonal titre of JHB3 and JH III in the pupariating 3rd instar larvae of GAL4-ptc.bantam and GAL4-ptc (control) were measured by adapting a protocol from a previous study [30]. In brief, sixty 3rd instar larvae from each group were collected, washed with distilled water and placed in stainless steel grinding jars containing balls of Retsch MM400.…”

Section: (C) Fly Cultures Mutants Construction Taqman Tm Microrna Amentioning

confidence: 99%

MicroRNAs regulate the sesquiterpenoid hormonal pathway inDrosophilaand other arthropods

Bendena

Nong

et al. 2017

Proc. R. Soc. B.

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Arthropods comprise the majority of all described animal species, and understanding their evolution is a central question in biology. Their developmental processes are under the precise control of distinct hormonal regulators, including the sesquiterpenoids juvenile hormone (JH) and methyl farnesoate. The control of the synthesis and mode of action of these hormones played important roles in the evolution of arthropods and their adaptation to diverse habitats. However, the precise roles of non-coding RNAs, such as microRNAs (miRNAs), controlling arthropod hormonal pathways are unknown. Here, we investigated the miRNA regulation of the expression of the juvenile hormone acid methyltransferase gene (), which encodes a rate-determining sesquiterpenoid biosynthetic enzyme. Loss of function of the miRNA in the fly increased expression, while overexpression of the repressed expression and resulted in pupal lethality. The male genital organs of the pupae were malformed, and exogenous sesquiterpenoid application partially rescued the genital deformities. The role of the in the regulation of sesquiterpenoid biosynthesis was validated by transcriptomic, qPCR and hormone titre (JHB3 and JH III) analyses. In addition, we found a conserved set of miRNAs that interacted with , and the sesquiterpenoid receptor methoprene-tolerant () in different arthropod lineages, including insects (fly, mosquito and beetle), crustaceans (water flea and shrimp), myriapod (centipede) and chelicerate (horseshoe crab). This suggests that these miRNAs might have conserved roles in the post-transcriptional regulation of genes in sesquiterpenoid pathways across the Panarthropoda. Some of the identified lineage-specific miRNAs are potential targets for the development of new strategies in aquaculture and agricultural pest control.

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Section: (C) Fly Cultures Mutants Construction Taqman Tm Microrna Amentioning

confidence: 99%

MicroRNAs regulate the sesquiterpenoid hormonal pathway inDrosophilaand other arthropods

Bendena

Nong

et al. 2017

Proc. R. Soc. B.

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“…Compound (Z)‐7g was found to be fast‐acting, inducing body tremors within 90 min after injection, characteristic of a neurological mode of action and not that of an HMG‐CoA reductase inhibitor, which would shut down juvenile hormone production and exhibit symptoms of other insect growth regulators (e.g. larval deformities and decreased egg viability) …”

Section: Resultsmentioning

confidence: 99%

Synthesis, stability and insecticidal activity of 2‐arylstilbenes

Horty

Daeuble

Castetter

et al. 2019

Pest Management Science

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BACKGROUND: A chemical scaffold-hopping approach from known 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors identified (E/Z)-2-arylstilbenes as novel insecticidal hits against two lepidopteran species, Spodoptera exigua and Trichoplusia ni. A structure-activity relationship (SAR) study of the aryl substituents and the E/Z conformations was carried out in an effort to improve insecticidal potency. RESULTS:A series of (E/Z)-2-arylstilbenes was prepared and separated to evaluate their insecticidal potency against lepidopterous species in diet-feeding assays. The results showed that the (Z)-2-arylstilbenes were more active than their corresponding (E)-isomers, and a stereoselective synthesis was utilized to expand the SAR of the (Z)-2-arylstilbenes. (Z)-4'-Fluoro-3 ′ -methyl-2-(2,4-difluorostyryl)-4-fluoro-5-methoxy-1,1 ′ -biphenyl was the most potent analog in this study with strong activity against S. exigua, T. ni, Helicoverpa zea, Plutella xylostella and Pseudoplusia includens.CONCLUSION: The (Z)-2-arylstilbenes were found to have strong insecticidal potency against five lepidopteran species. Ultimately, synthetic efforts could not improve insecticidal potency to commercial levels, and a lack of UV stability led to efforts being discontinued.

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“…Each group had three independent pools of five animals run in triplicate and normalized to β‐actin. Rates of JH synthesis following RNAi treatment were measured using gas chromatography tandem mass spectrometry as described previously …”

Section: Methodsmentioning

confidence: 99%

“…Geranylgeraniol, sinefungin and clotrimazole are inhibitors of FOLD, JHAMT and CYP15C1. These inhibitors were assayed to determine whether these candidate genes could be potential insecticide targets using the JH in vitro biosynthetic assay described previously . Geranylgeraniol, sinefungin and clotrimazole (Sigma‐Aldrich, St. Louis, MO, USA) were dissolved in medium 199 (final concentration 10 μM) for the JH biosynthesis assay.…”

Section: Methodsmentioning

confidence: 99%

“…These inhibitors were assayed to determine whether these candidate genes could be potential insecticide targets using the JH in vitro biosynthetic assay described previously. 12 Geranylgeraniol, sinefungin and clotrimazole (Sigma-Aldrich, St. Louis, MO, USA) were dissolved in medium 199 (final concentration 10 μM) for the JH biosynthesis assay. Each pair of CA was incubated for 3 h at 30 ∘ C in 100 μL of medium 199 with inhibitors in the dark with gentle shaking.…”

Section: Assays Of Related Jh Biosynthetic Enzyme Inhibitors 261 Asmentioning

confidence: 99%

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Enzymes in the juvenile hormone biosynthetic pathway can be potential targets for pest control

Yin

Qiu

Huang

et al. 2019

Pest Management Science

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BACKGROUND Discovery of novel insecticides and targets has received global attention in recent years. Ten genes coding for enzymes involved in the juvenile hormone biosynthetic pathway of Manduca sexta were studied as potential insecticide targets. RESULTS We determined the expression of genes encoding some critical enzymes in the JH biosynthetic pathway. Farnesol dehydrogenase (FOLD), Juvenile hormone acid O‐methyltransferase (JHAMT) and Juvenile hormone epoxidase (CYP15C1) were selected as the candidate targets based on gene expression results. RNAi silencing and enzyme inhibitor tests were performed to validate whether these candidate genes could be the potential insecticide targets. The down‐regulation of FOLD, JHAMT and CYP15C1 resulted in a 68%, 82% and 79% reduction in the rates of JH biosynthesis in vitro, respectively. In addition, RNA interference and inhibitor studies of these enzymes following oral administration demonstrated the potential application in pest management, with respect to high mortality and effects on growth. CONCLUSION Based on our study, FOLD, JHAMT and CYP15C1 could be potential targets for pest control as a consequence of their important roles in insect development. © 2019 Society of Chemical Industry

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Discovery and quantitative structure–activity relationship study of lepidopteran HMG‐CoA reductase inhibitors as selective insecticides

Cited by 10 publications

References 27 publications

MicroRNAs regulate the sesquiterpenoid hormonal pathway inDrosophilaand other arthropods

MicroRNAs regulate the sesquiterpenoid hormonal pathway inDrosophilaand other arthropods

Synthesis, stability and insecticidal activity of 2‐arylstilbenes

Enzymes in the juvenile hormone biosynthetic pathway can be potential targets for pest control

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