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1.
Sci Rep ; 14(1): 4308, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383681

RESUMO

The fall armyworm (FAW) Spodoptera frugiperda is a severe economic pest of multiple crops globally. Control of this pest is often achieved using insecticides; however, over time, S. frugiperda has developed resistance to new mode of action compounds, including diamides. Previous studies have indicated diamide resistance is a complex developmental process involving multiple detoxification genes. Still, the mechanism underlying the possible involvement of microRNAs in post-transcriptional regulation of resistance has not yet been elucidated. In this study, a global screen of microRNAs (miRNAs) revealed 109 known and 63 novel miRNAs. Nine miRNAs (four known and five novel) were differentially expressed between insecticide-resistant and -susceptible strains. Gene Ontology analysis predicted putative target transcripts of the differentially expressed miRNAs encoding significant genes belonging to detoxification pathways. Additionally, miRNAs are involved in response to diamide exposure, indicating they are probably associated with the detoxification pathway. Thus, this study provides comprehensive evidence for the link between repressed miRNA expression and induced target transcripts that possibly mediate diamide resistance through post-transcriptional regulation. These findings highlight important clues for further research to unravel the roles and mechanisms of miRNAs in conferring diamide resistance.


Assuntos
Inseticidas , MicroRNAs , Animais , Spodoptera/genética , MicroRNAs/genética , Diamida/farmacologia , Inseticidas/farmacologia , Regulação da Expressão Gênica , Resistência a Inseticidas/genética , Larva
2.
Front Immunol ; 15: 1295150, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384456

RESUMO

Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with Salmonella typhimurium. The scavenging of mitochondrial reactive oxygen species by mitochondria-targeted antioxidants MitoQ and SkQ1, as well as inhibition of their production by mitochondrial inhibitors, inhibit the synthesis of leukotrienes regardless of the cessation of oxidative phosphorylation. On the contrary, antioxidants N-acetylcysteine and sodium hydrosulfide promoting reductive shift in the reversible thiol-disulfide system stimulate the synthesis of leukotrienes. Diamide that oxidizes glutathione at high concentrations inhibits leukotriene synthesis, and the glutathione precursor S-adenosyl-L-methionine prevents this inhibition. Diamide-dependent inhibition is also prevented by diphenyleneiodonium, presumably through inhibition of NADPH oxidase and NADPH accumulation. Thus, during bacterial infection, maintaining the reduced state of glutathione in neutrophils plays a decisive role in the synthesis of leukotriene B4. Suppression of excess leukotriene synthesis is an effective strategy for treating various inflammatory pathologies. Our data suggest that the use of mitochondria-targeted antioxidants may be promising for this purpose, whereas known thiol-based antioxidants, such as N-acetylcysteine, may dangerously stimulate leukotriene synthesis by neutrophils during severe pathogenic infection.


Assuntos
Leucotrieno B4 , Neutrófilos , Salmonella typhimurium , Acetilcisteína/farmacologia , Diamida/farmacologia , Leucotrienos/farmacologia , Fatores Quimiotáticos , Oxirredução , Antioxidantes/farmacologia , Glutationa/farmacologia , Compostos de Sulfidrila/farmacologia
3.
PLoS One ; 19(2): e0295928, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394153

RESUMO

The fall armyworm (Spodoptera frugiperda) is one of the most destructive pests of corn. New infestations have been reported in the East Hemisphere, reaching India, China, Malaysia, and Australia, causing severe destruction to corn and other crops. In Puerto Rico, practical resistance to different mode of action compounds has been reported in cornfields. In this study, we characterized the inheritance of resistance to chlorantraniliprole and flubendiamide and identified the possible cross-resistance to cyantraniliprole and cyclaniliprole. The Puerto Rican (PR) strain showed high levels of resistance to flubendiamide (RR50 = 2,762-fold) and chlorantraniliprole (RR50 = 96-fold). The inheritance of resistance showed an autosomal inheritance for chlorantraniliprole and an X-linked inheritance for flubendiamide. The trend of the dominance of resistance demonstrated an incompletely recessive trait for H1 (♂ SUS × â™€ PR) × and an incompletely dominant trait for H2 (♀ SUS × â™‚ PR) × for flubendiamide and chlorantraniliprole. The PR strain showed no significant presence of detoxification enzymes (using synergists: PBO, DEF, DEM, and VER) to chlorantraniliprole; however, for flubendiamide the SR = 2.7 (DEM), SR = 3.2 (DEF) and SR = 7.6 (VER) indicated the role of esterases, glutathione S- transferases and ABC transporters in the metabolism of flubendiamide. The PR strain showed high and low cross-resistance to cyantraniliprole (74-fold) and cyclaniliprole (11-fold), respectively. Incomplete recessiveness might lead to the survival of heterozygous individuals when the decay of diamide residue occurs in plant tissues. These results highlight the importance of adopting diverse pest management strategies, including insecticide rotating to manage FAW populations in Puerto Rico and other continents.


Assuntos
Fluorocarbonos , Inseticidas , Mariposas , Ftalimidas , Pirazóis , Sulfonas , ortoaminobenzoatos , Humanos , Animais , Spodoptera/genética , Diamida/farmacologia , Porto Rico , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Larva
4.
Int J Mol Sci ; 25(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38397120

RESUMO

Diamide insecticides have always been a hot research topic in the field of pesticides. To further discover new compounds with high activity and safety, indane and its analogs were introduced into chlorantraniliprole, and a battery of chlorfenil derivatives, including indane and its analogs, were designed and prepared for biological testing. Their characterization and verification were carried out through nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Biological detection showed that all the compounds exhibited good insecticidal activity against Mythimna separata. At 0.8 mg/L, the insecticidal activity of compound 8q against Mythimna separata was 80%, which was slightly better than that of chlorantraniliprole. The results of the structure-activity relationship (SAR) analysis indicated that the indane moiety had a significant effect on insecticidal activity, especially in the R-configuration. The results indicated that chlorantraniliprole derivatives containing indane groups could serve as pilot compounds for the further development of new insecticides.


Assuntos
Inseticidas , Mariposas , ortoaminobenzoatos , Animais , Inseticidas/química , Diamida/farmacologia , Desenho de Fármacos , Relação Estrutura-Atividade , Estrutura Molecular
5.
Talanta ; 270: 125620, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38176249

RESUMO

Efficiently detecting diamide insecticides in environmental water is challenging due to their low concentrations and complex matrix interferences. In this study, we developed ionic liquids (ILs)-incorporated magnetic molecularly imprinted polymers (IL-MMIPs) for the detection of diamide insecticides, capitalizing on the advantages of ILs and quick magnetic separation through surface imprinting. Tetrachlorantraniliprole was used as the template, and a specific IL, 1-vinyl-3-ethylimidazolium hexafluorophosphate ([VEIm][PF6]), was employed as the functional monomer. Various synthesis conditions were investigated to optimize adsorption efficiency. The prepared IL-MMIPs were successfully employed as adsorbents in magnetic solid-phase extraction (MSPE) to selectively extract, separate, and quantify three types of diamide insecticides from water samples using HPLC-UV detection. Under optimal conditions, the analytical method achieved low limits of detection (0.69 ng mL-1, 0.64 ng mL-1, 0.59 ng mL-1 for cyantraniliprole, chlorantraniliprole and tetrachlorantraniliprole, respectively). The method also displayed a wide linear range (0.003-10 µg mL-1 for cyantraniliprole and chlorantraniliprole, and 0.004-10 µg mL-1 for tetrachlorantraniliprole, respectively) with satisfactory coefficients (R2≥0.9996), and low relative standard deviation (RSD≤2.55%). Additionally, extraction recoveries fell within the range of 79.4%-109%. The results clearly demonstrate that IL-MMIPs exhibit exceptional recognition and rebinding capabilities. The developed IL-MMIPs-MSPE-HPLC-UV method is straightforward and rapid, making it suitable for the detection and analysis of three kinds of diamide insecticides in environmental water.


Assuntos
Inseticidas , Líquidos Iônicos , Impressão Molecular , Pirazóis , ortoaminobenzoatos , Água , Polímeros Molecularmente Impressos , Diamida , Impressão Molecular/métodos , Cromatografia Líquida de Alta Pressão , Polímeros , Adsorção , Fenômenos Magnéticos , Extração em Fase Sólida/métodos
6.
Talanta ; 270: 125626, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38211354

RESUMO

This study presents a novel, eco-friendly composite adsorbent material designed for the magnetic solid-phase extraction of diamide insecticides from vegetable samples. The membrane, denoted as Fe-MMm, was incorporated with a cellulose framework embedded with Metal-Organic Frameworks (MOFs) and Multi-Walled Carbon Nanotubes (MWCNTs) magnetized with Fe3O4. This innovative material streamlined the conventional solid-phase extraction process, simplifying the sample pre-treatment. By combining it with liquid chromatography tandem mass spectrometry (LC-MS/MS), the method achieves significantly enhanced extraction efficiency through systematic optimization of experimental parameters, including adsorbent selection, pH, ionic strength, adsorption time, and elution time. The method had a wide linear range of 0.1-1000 ng/mL and an exceptionally low detection limit ranging from 0.023 to 0.035 ng/mL. The successful identification of diamide insecticides in vegetable samples underscores the potential of Fe-MMm as a robust material for sample pretreatment in analytical applications.


Assuntos
Inseticidas , Nanotubos de Carbono , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Verduras/química , Diamida , Espectrometria de Massas em Tandem/métodos , Nanotubos de Carbono/química , Extração em Fase Sólida/métodos , Limite de Detecção
7.
Environ Toxicol Chem ; 43(2): 429-439, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37991213

RESUMO

Diamide insecticides are widely used in rice paddies and pose a potential threat to aquatic organisms. However, the risk research related to their application in major rice-producing areas is very limited, especially mesocosm research to simulate the impact on aquatic ecosystems of long-term exposure, as well as exposure analysis based on local models and local scenarios. To assess potential risks from a novel diamide insecticide (tetrachlorantraniliprole) to aquatic nontarget organisms in the field over long-term exposure, an outdoor mesocosm study was performed, and the environmental concentrations were predicted by the multimedia paddy-pond model (TOPRICE). The mesocosm experiment showed that tetrachlorantraniliprole mainly stayed in the aqueous phase after entering the water body. Although the chemical dissipated quickly in the aqueous phase (half-life of 0.79-1.5 days), it showed toxic effects on zooplankton communities. Cladocerans, represented by Simocephalus vetulus, were most sensitive to tetrachlorantraniliprole stress. Significant short-term toxicity to cladocerans occurred in all treatment groups, but all recovered within 8 weeks except for the highest concentration group (30.0 µg /L). Based on the ecological recovery results, 7.74 µg tetrachlorantraniliprole/L (nominal concentration, 10.0 µg /L) is suggested to be the no-observed-ecological-adverse-effect concentration (NOEAEC) for the zooplankton community. When this NOEAEC was compared with predicted environmental concentrations (PECs; the PECs in natural ponds simulated by the TOPRICE model for 148 application scheme combinations in major rice-producing areas), a relatively high risk of applying tetrachlorantraniliprole during the rice tillering stage was found. The present study makes a positive contribution to the hypothesis that the current Tier 1 approaches for global acute risk assessment have a sufficient protective effect for assessing the risk of tetrachlorantraniliprole to aquatic organisms. Also, the present results should help us to gain a fuller understanding of the ecological risk of diamide insecticides in aquatic ecosystems and their rational application schemes. Environ Toxicol Chem 2024;43:429-439. © 2023 SETAC.


Assuntos
Inseticidas , Oryza , Poluentes Químicos da Água , Animais , Inseticidas/toxicidade , Ecossistema , Zooplâncton , Diamida/farmacologia , Organismos Aquáticos , Poluentes Químicos da Água/toxicidade
8.
J Insect Sci ; 23(6)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38055941

RESUMO

The nest-scavenging beetle Aethina tumida remains a persistent problem for beekeepers in parts of the Southeast United States, where warm wet soils allow beetle populations to grow rapidly and overwhelm colonies, especially during the summer dearth. Furthermore, small hive beetle infestation prevents beekeepers from easily provisioning colonies with additional pollen or protein feed (patties), preventing holistic management of honey bee health via improved nutrition, and reducing the economic potential of package and nucleus colony rearing in the Southeast. Here, we demonstrate using both in vitro laboratory trials and a small in vivo field trial that the differential specificity of anthranilic diamide insecticides (specifically, chlorantraniliprole) between bees and beetles allows for the control and prevention of small hive beetle infestation in honey bee colonies even when feeding with large patties. Honey bees show orders of magnitude higher tolerance to chlorantraniliprole compared to small hive beetles, opening new avenues for improving bee health including during spring splits and throughout the summer.


Assuntos
Abelhas , Besouros , Inseticidas , ortoaminobenzoatos , Animais , Abelhas/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Besouros/efeitos dos fármacos , Diamida , Himenópteros/efeitos dos fármacos , Inseticidas/farmacologia , ortoaminobenzoatos/farmacologia
9.
J Med Chem ; 66(24): 17086-17104, 2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38079537

RESUMO

A set of focused analogues have been generated around a lead indirect adenosine monophosphate-activated kinase (AMPK) activator to improve the rat clearance of the molecule. Analogues were focused on inhibiting amide hydrolysis by the strategic placement of substituents that increased the steric environment about the secondary amide bond between 4-aminopiperidine and pyridine-5-carboxylic acid. It was found that placing substituents at position 3 of the piperidine ring and position 4 of the pyridine could all improve clearance without significantly impacting on-target potency. Notably, trans-3-fluoropiperidine 32 reduced rat clearance from above liver blood flow to 19 mL/min/kg and improved the hERG profile by attenuating the basicity of the piperidine moiety. Oral dosing of 32 activated AMPK in mouse liver and after 2 weeks of dosing improved glucose handling in a db/db mouse model of Type II diabetes as well as lowering fasted glucose and insulin levels.


Assuntos
Diabetes Mellitus Tipo 2 , Camundongos , Ratos , Animais , Proteínas Quinases Ativadas por AMP , Diamida , Glucose , Piridinas/farmacologia , Piperidinas , Amidas
10.
J Agric Food Chem ; 71(46): 17646-17657, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37939255

RESUMO

Diamide insecticides have gained popularity due to their high efficacy and low toxicity to nontarget organisms. However, diamide-associated resistance has emerged recently, causing a significant reduction in their potency, thereby hindering sustainable agricultural development. Here, we explored novel diamide insecticide analogs and, using a structure-based approach, rationally designed and synthesized 28 nitrophenyl substituted anthranilic diamides. Most of the compounds showed moderate to good activity against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compounds Ia and Im showed extraordinarily high activity and their mode of action was verified on isolated neurons. Additionally, Im exhibited over 10-fold greater potency than chlorantraniliprole in a HEK293 cell line stably expressing S. frugiperda ryanodine receptors (SfRyRs) containing the resistance mutations, G4891E and I4734M. The binding modes of Im in the SfRyRs were predicted using in silico molecular docking analysis. Our novel nitrophenyl substituted anthranilic diamide derivatives provide valuable insights for the design of insecticidal RyR-targeting compounds to effectively control both wild type and diamide insecticide-resistant lepidopteran pests.


Assuntos
Inseticidas , Mariposas , Animais , Humanos , Diamida/farmacologia , Simulação de Acoplamento Molecular , Células HEK293 , Mariposas/genética , Spodoptera/metabolismo , Inseticidas/farmacologia , Inseticidas/química , ortoaminobenzoatos/farmacologia , ortoaminobenzoatos/química , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Resistência a Inseticidas/genética
11.
Microbiol Spectr ; 11(6): e0160823, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37819171

RESUMO

IMPORTANCE: During their life cycle, bacteria are exposed to a range of different stresses that need to be managed appropriately in order to ensure their growth and viability. This applies not only to bacteria in their natural habitats but also to bacteria employed in biotechnological production processes. Oxidative stress is one of these stresses that may originate either from bacterial metabolism or external factors. In biotechnological settings, it is of critical importance that production strains are resistant to oxidative stresses. Accordingly, this also applies to the major industrial cell factory Bacillus subtilis. In the present study, we, therefore, developed a screen for B. subtilis strains with enhanced oxidative stress tolerance. The results show that our approach is feasible and time-, space-, and resource-efficient. We, therefore, anticipate that it will enhance the development of more robust industrial production strains with improved robustness under conditions of oxidative stress.


Assuntos
Bacillus , Bacillus/genética , Bacillus/metabolismo , Diamida/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Estresse Oxidativo , Fenótipo , Proteínas de Bactérias/genética
12.
Pestic Biochem Physiol ; 195: 105579, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37666604

RESUMO

Since 2007, diamide insecticides have been widely used in Korea to control various types of lepidopteran pests including Spodoptera exigua. For nearly a decade, diamide resistance in field populations of S. exigua across 18 localities has been monitored using bioassays. Despite their short history of use, resistance to diamide insecticides has emerged. Based on the LC50 values, some field populations showed a higher level of resistance to chlorantraniliprole, a diamide insecticide, compared to that of the susceptible strain, although regional and temporal variations were observed. To investigate resistance at a molecular level, we examined three mutations (Y4701C, I4790M, and G4946E) in the ryanodine receptor (RyR), which is the primary mechanism underlying diamide insecticide resistance. DNA sequencing showed that only the I4790M mutation was found in most field populations. As resistance levels varied significantly despite the uniform presence of the I4790M mutation, we considered the presence of another resistance factor. Further, the I4790M mutation was also found in S. exigua specimens collected prior to the commercialization of diamide insecticides in Korea as well as in other countries, such as the USA. This finding led us to hypothesize that the I4790M mutation were predisposed in field populations owing to selection factors other than diamide use. For further clarification, we conducted whole-genome sequencing of S. exigua (449.83 Mb) and re-sequencing of 18 individual whole genomes. However, no additional non-synonymous mutations were detected in the RyR-coding region. Therefore, we concluded that the high level of diamide insecticide resistance in Korean S. exigua is not caused by mutations at the target site, RyR, but is attributed to other factors that need to be investigated in future studies.


Assuntos
Inseticidas , Canal de Liberação de Cálcio do Receptor de Rianodina , Animais , Spodoptera/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Museus , Diamida/farmacologia , Inseticidas/farmacologia
13.
J Agric Food Chem ; 71(39): 14137-14150, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37733789

RESUMO

The research and development of organofluorine chemistry has flourished; in particular, monofluoroalkene has aroused considerable interest from medicinal and organic chemists. It is a significant attempt to introduce monofluoroalkene into agrochemicals. In this study, monofluoroalkene was introduced into diamide molecules and inserted between the aliphatic amide and benzene ring, and 44 compounds have been successfully synthesized. The bioassay results showed that compounds with monofluoro-acrylamide moiety (Z-isomers) had excellent larvicidal activity against lepidopteran pests at 5 mg·L-1. The LC50 values of compounds B16, B18, and B21 against Mythimna separata were 1.02, 1.32, and 0.78 mg·L-1, respectively. 3D-QSAR analysis including the CoMFA model and the CoMSIA model was conducted to illustrate the contributions of steric, electrostatic, hydrophobic, and hydrogen bond fields on the bioactivity. Moreover, typical symptoms caused by chlorantraniliprole including dehydration, shrinkage, and blackening were also observed on the test larvae treated with monofluoro-acrylamide diamide compounds. M. separata central neurons calcium imaging experiment of compound B18 indicated that the monofluoro-acrylamide diamide compounds were potential insect ryanodine receptor activators. The molecular docking was performed in the CHL binding domain of Plutella xylostella RyR and revealed that the predicted binding mode of compound B21 was slightly different from that of CHL. The MM|GBSA dG Bind values of B21 and CHL with P. xylostella RyR were respectively -85.797 and -95.641 kcal·mol-1. The present work explored the insecticidal properties of a new diamide scaffold containing a monofluoro-acrylamide fragment and extended the application of monofluoroalkene in the agrochemical field.


Assuntos
Inseticidas , Mariposas , Animais , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Diamida/farmacologia , Diamida/química , Acrilamidas , Simulação de Acoplamento Molecular , Mariposas/metabolismo , Inseticidas/farmacologia , Inseticidas/química , Acrilamida , ortoaminobenzoatos/química
14.
Int J Mol Sci ; 24(15)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37569900

RESUMO

The spermatozoa have limited antioxidant defences, a high polyunsaturated fatty acids content and the impossibility of synthesizing proteins, thus being susceptible to oxidative stress. High levels of reactive oxygen species (ROS) harm human spermatozoa, promoting oxidative damage to sperm lipids, proteins and DNA, leading to infertility. Coenzyme A (CoA) is a key metabolic integrator in all living cells. Recently, CoA was shown to function as a major cellular antioxidant mediated by a covalent modification of surface-exposed cysteines by CoA (protein CoAlation) under oxidative or metabolic stresses. Here, the profile of protein CoAlation was examined in sperm capacitation and in human spermatozoa treated with different oxidizing agents (hydrogen peroxide, (H2O2), diamide and tert-butyl hydroperoxide (t-BHP). Sperm viability and motility were also investigated. We found that H2O2 and diamide produced the highest levels of protein CoAlation and the greatest reduction of sperm motility without impairing viability. Protein CoAlation levels are regulated by 2-Cys peroxiredoxins (PRDXs). Capacitated spermatozoa showed lower levels of protein CoAlation than non-capacitation cells. This study is the first to demonstrate that PRDXs regulate protein CoAlation, which is part of the antioxidant response of human spermatozoa and participates in the redox regulation associated with sperm capacitation.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Humanos , Masculino , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Diamida/metabolismo , Motilidade dos Espermatozoides , Sêmen/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/metabolismo , Peroxirredoxinas/metabolismo
15.
Pest Manag Sci ; 79(12): 5260-5269, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37599274

RESUMO

BACKGROUND: Agricultural pests have caused huge losses in agricultural production and threaten global food security. Synthetic insecticides remain the major control method. However, with the rapid development of pest resistance and the increasingly stringent regulations on pesticide usage, the development of efficient insecticides with novel structures is particularly urgent. RESULTS: Twenty-six novel anthranilic diamide derivatives containing the thiazole moiety were designed based on the scaffold hopping strategy. Bioassay results indicated that compound 6e exhibited excellent insecticidal activity against a susceptible strain of diamondback moth (Plutella xylostella) with a median lethal concentration (LC50 ) of 0.65 mg L-1 , which was similar to chlorantraniliprole (LC50 = 0.53 mg L-1 ). Compound 6e showed marginally lower (LC50 = 50.45 mg L-1 ) insecticidal activity than chlorantraniliprole (LC50 = 31.98 mg L-1 ) on chlorantraniliprole-resistant P. xylostella larvae, suggesting a cross-resistance of compound 6e with chlorantraniliprole (resistance ratios, 77.6-fold and 60.3-fold, respectively). Compound 6e also showed good insecticidal activity against fall armyworm and beet armyworm with pest mortalities of 74% and 64%, respectively, at 5 mg L-1 concentration. In addition, compounds 6e and 12a showed delayed toxicity against red imported fire ant with mortality rates of 84% and 85% (respectively) after 5 days of treatment at 1.0 mg L-1 , which were superior to that of chlorantraniliprole. CONCLUSION: The introduction of thiazole into anthranilic diamide scaffolds resulted in insecticidal leads 6e and 12a with excellent insecticidal activities and potential application in controlling red imported fire ants. The work also guides the discovery of insecticidal molecules with thiazole-containing anthranilic diamide scaffold. © 2023 Society of Chemical Industry.


Assuntos
Inseticidas , Mariposas , Animais , Inseticidas/farmacologia , Inseticidas/química , Relação Estrutura-Atividade , Diamida/farmacologia , Diamida/química , Larva , Tiazóis/farmacologia
16.
Phytochemistry ; 214: 113792, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37454887

RESUMO

Phytochemical study on the methanol extract of Aglaia odorata leaves resulted in the isolation of four previously undescribed compounds, including three 2,9-deoxyflavonoids and one flavonol-diamide [3 + 2] adduct, and 13 known compounds. The chemical structures of the four undescribed compounds were elucidated on the basis of their IR, HR-ESI-MS, 1D and 2D NMR, and ECD spectra. The results revealed an unprecedented 2,9-deoxyflavonoid framework, which was confirmed by TD-DFT, ECD, and GIAO 13C-NMR calculations using sorted training set methods. The 17 compounds were examined for their ability to inhibit NO production activity in cultured lipopolysaccharide-activated RAW264.7 cells with aglaodoratas A-C, odorine, and epi-odorine inhibiting NO production, with IC50 values in the range of 16.2-24.3 µM. The other investigated compounds had either weak or no activity.


Assuntos
Aglaia , Aglaia/química , Diamida/análise , Óxido Nítrico , Extratos Vegetais/química , Folhas de Planta/química , Estrutura Molecular
17.
J Agric Food Chem ; 71(29): 11001-11007, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37462137

RESUMO

Ryanodine receptor (RyR) has been used as an insecticide target to control many destructive agricultural pests. The effectiveness of these insecticides has been limited by the spread of resistance mutations identified in pest RyRs, but the detailed molecular impacts of the individual mutations on the activity of different diamide compounds have not been fully explored. We created five HEK293 cell lines stably expressing wild type rabbit RyR1, wild type Spodoptera frugiperda RyR (Sf RyR), or Sf RyR carrying different resistance mutations, including G4891E, G4891E/I4734M, and Y4867F, respectively. R-CEPIA1er, a genetically encoded fluorescent protein, was also introduced in these cell lines to report the Ca2+ concentration in the endoplasmic reticulum. We systematically characterized the activities of six commercial diamide insecticides against different RyRs using the time-lapse fluorescence assay. Among them, cyantraniliprole (CYAN) displayed the highest activity against all three resistant Sf RyRs. The good performance of CYAN was confirmed by the toxicity assay using gene-edited Drosophila expressing the mutant RyRs, in which CYAN showed the lowest LD50 value for the double resistant mutant. In addition, we compared their acitivty between mammalian and insect RyRs and found that flubendiamide has the best insect-selectivity. The mechanism of the anti-resistance property and selectivity of the compounds was proposed based on the structural models generated by homology modeling and molecular docking. Our findings provide insights into the mechanism of insect resistance and guidance for developing effective RyR agonists that can selectively target resistant pests.


Assuntos
Inseticidas , Mariposas , Humanos , Animais , Coelhos , Inseticidas/farmacologia , Inseticidas/química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Diamida/farmacologia , Simulação de Acoplamento Molecular , Células HEK293 , Resistência a Inseticidas/genética , Mariposas/genética , Mariposas/metabolismo , Mamíferos/metabolismo
18.
Int J Mol Sci ; 24(12)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37373410

RESUMO

A reaction of acyl chlorides derived from 1,10-phenanthroline-2,9-dicarboxylic acids with piperazine allows the preparation of the corresponding 24-membered macrocycles in good yield. The structural and spectral properties of these new macrocyclic ligands were thoroughly investigated, revealing promising coordination properties towards f-elements (Am, Eu). It was shown that the prepared ligands can be used for selective extraction of Am(III) from alkaline-carbonate media in presence of Eu(III) with an SFAm/Eu up to 40. Their extraction efficiency is higher than calixarene-type extraction of the Am(III) and Eu(III) pair. Composition of macrocycle-metal complex with Eu(III) was investigated by luminescence and UV-vis spectroscopy. The possibility of such ligands to form complexes of L:Eu = 1:2 stoichiometry is revealed.


Assuntos
Complexos de Coordenação , Diamida , Modelos Moleculares , Ligantes , Complexos de Coordenação/química
19.
Insect Biochem Mol Biol ; 159: 103983, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37380137

RESUMO

The tomato leafminer, Tuta absoluta, is an invasive crop pest that has evolved resistance to many of the insecticides used for its control. To facilitate the investigation of the underpinning mechanisms of resistance in this species we generated a contiguous genome assembly using long-read sequencing data. We leveraged this genomic resource to investigate the genetic basis of resistance to the diamide insecticide chlorantraniliprole in Spanish strains of T. absoluta that exhibit high levels of resistance to this insecticide. Transcriptomic analyses revealed that, in these strains, resistance is not associated with previously reported target-site mutations in the diamide target-site, the ryanodine receptor, but rather is associated with the marked overexpression (20- to >100-fold) of a gene encoding a UDP-glycosyltransferase (UGT). Functional expression of this UGT, UGT34A23, via ectopic expression in Drosophila melanogaster demonstrated that it confers strong and significant resistance in vivo. The genomic resources generated in this study provide a powerful resource for further research on T. absoluta. Our findings on the mechanisms underpinning resistance to chlorantraniliprole will inform the development of sustainable management strategies for this important pest.


Assuntos
Inseticidas , Lepidópteros , Mariposas , Solanum lycopersicum , Animais , Inseticidas/farmacologia , Diamida , Resistência a Inseticidas/genética , Drosophila melanogaster , Difosfato de Uridina
20.
J Toxicol Environ Health A ; 86(15): 518-533, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37306479

RESUMO

The present study examined the acute and chronic toxicity attributed to commercial formulations of the anthranilic diamide insecticides chlorantraniliprole (CHLO) and cyantraniliprole (CYAN) on the neotropical amphibian species Rhinella arenarum, Rhinella fernandezae and Scinax granulatus. The median lethal concentrations obtained after 96 hr exposure (96 hr-LC50) were generally greater than 100 mg/L, except for stage 25 S. Granulatus, which were the most sensitive animals tested with a 96 hr-LC50 value of 46.78 mg/L. In subchronic exposures of R. arenarum, the 21day-LC50 were 151.4 mg/L for CHLO and >160 mg/L for CYAN, the weight gain of the tadpoles during this period not being markedly affected in both cases. Finally, when tadpoles of R. arenarum were exposed to CHLO throughout the metamorphic process, an inverted U-shaped non-monotonic dose-response relationship was observed between exposure concentrations and both % of individuals transiting between stage 39 and 42 and the time required to accomplish this. Data obtained raise the hypothesis of an effect of CHLO on the hypothalamic-pituitary-thyroid (HPT) axis, either directly or through an interaction with the stress-hormone system, as metamorphic progression from stage 39 to S42 occurs under the strict control of thyroid hormones. These observations are important as the anthranilic diamide insecticides are not currently known as endocrine disruptors. Further investigations are needed to clarify the pathways leading to these effects and examine whether environmentally-relevant aquatic concentrations of anthranilic diamides might be impacting amphibian populations in the wild.


Assuntos
Inseticidas , Animais , Larva , Inseticidas/toxicidade , Diamida/toxicidade , Anuros
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