RESUMEN
The intermediate filament protein vimentin performs an essential role in cytoskeletal interplay and dynamics, mechanosensing and cellular stress responses. In pathology, vimentin is a key player in tumorigenesis, fibrosis and infection. Vimentin filaments undergo distinct and versatile reorganizations, and behave as redox sensors. The vimentin monomer possesses a central α-helical rod domain flanked by N- and C-terminal low complexity domains. Interactions between this type of domains play an important function in the formation of phase-separated biomolecular condensates, which in turn are critical for the organization of cellular components. Here we show that several oxidants, including hydrogen peroxide and diamide, elicit the remodeling of vimentin filaments into small particles. Oxidative stress elicited by diamide induces a fast dissociation of filaments into circular, motile dots, which requires the presence of the single vimentin cysteine residue, C328. This effect is reversible, and filament reassembly can occur within minutes of oxidant removal. Diamide-elicited vimentin droplets recover fluorescence after photobleaching. Moreover, fusion of cells expressing differentially tagged vimentin allows the detection of dots positive for both tags, indicating that vimentin dots merge upon cell fusion. The aliphatic alcohol 1,6-hexanediol, known to alter interactions between low complexity domains, readily dissolves diamide-elicited vimentin dots at low concentrations, in a C328 dependent manner, and hampers reassembly. Taken together, these results indicate that vimentin oxidation promotes a fast and reversible filament remodeling into biomolecular condensate-like structures, and provide primary evidence of its regulated phase separation. Moreover, we hypothesize that filament to droplet transition could play a protective role against irreversible damage of the vimentin network by oxidative stress.
Asunto(s)
Diamida , Peróxido de Hidrógeno , Filamentos Intermedios , Estrés Oxidativo , Vimentina , Vimentina/metabolismo , Humanos , Filamentos Intermedios/metabolismo , Diamida/farmacología , Peróxido de Hidrógeno/metabolismo , Condensados Biomoleculares/metabolismo , Condensados Biomoleculares/química , Oxidación-ReducciónRESUMEN
The effectiveness, tolerance, and safety of pesticides must be established before their scientific or rational. This study evaluates the field control efficacy of broflanilide, tetraniliprole, and chlorantraniliprole in combating Spodoptera frugiperda in maize crops, as well as the resistance of S. frugiperda to these three diamide pesticides after exposure. By assessing field control efficiency, toxicity, effects on development and reproduction, and detoxification enzyme activity of these diamide pesticides on S. frugiperda, highlights broflanilide's significant insecticidal potential. A highly sensitive and efficient method using QuEChERS/HPLCMS/MS was developed to simultaneously detect residues of these three pesticides on maize. Initial concentrations of broflanilide, tetraniliprole, and chlorantraniliprole ranged from 2.13 to 4.02â¯mg/kg, with their respective half-lives varying between 1.23 and 1.51 days. Following foliar application, by the time of harvest, the terminal residue concentrations of these pesticides were all under 0.01â¯mg/kg. Chronic dietary intake risk assessments and cumulative chronic dietary exposure for three pesticides indicated that the general population's terminal residue concentration was within acceptable limits. Not only does this research provide valuable insights into field control efficiency, insecticidal effects, resistance, residues, and risk assessment results of broflanilide, tetraniliprole, and chlorantraniliprole on maize, but additionally, it also paves the way for setting suitable Maximum Residue Limits (MRLs) values based on pre-harvest interval values, rational dosage, and application frequency.
Asunto(s)
Insecticidas , Spodoptera , Zea mays , ortoaminobenzoatos , Spodoptera/efectos de los fármacos , Animales , Insecticidas/toxicidad , Medición de Riesgo , ortoaminobenzoatos/toxicidad , Productos Agrícolas , Residuos de Plaguicidas/toxicidad , Residuos de Plaguicidas/análisis , Diamida/toxicidad , Larva/efectos de los fármacos , Resistencia a los InsecticidasRESUMEN
Antioxidants are widely used in medicine due to their ability to bind free radicals - active biomolecules that destroy the genetic apparatus of cells and the structure of their membranes, which makes it possible to reduce the intensity of oxidative processes in the body. In a living organism, free radicals are involved in various processes, but their activity is controlled by antioxidants. The purpose of this work was to conduct a series of studies to identify the antioxidant activity of new synthesized compounds of a series of oxalic acid diamides in the brain and liver tissue of white rats in vivo and in vitro experiments, as well as to determine their potential pharmacological properties. The studies were conducted on outbred white male rats, weighing 180-200 g, kept on a normal diet. After autopsy, the brain and liver were isolated, washed with saline, cleared of blood vessels, and homogenized in Tris-HCl buffer (pH-7.4) (in vitro). The research results showed significant antioxidant activity (AOA) of all compounds with varying effectiveness. The most pronounced activity was demonstrated by compound SV-425 in both brain and liver tissues. Compound SV-427 demonstrated the least activity, with levels in brain tissue and liver tissue. In addition, all physicochemical descriptors of the studied compounds comply with Lipinski's rule of five to identify new molecules for the treatment of oxidative stress. From the data obtained, it can be concluded that the studied compounds have antioxidant properties, helping to protect cells from oxidative stress. This is important for the prevention and treatment of diseases associated with increased levels of free radicals.
Asunto(s)
Antioxidantes , Encéfalo , Peroxidación de Lípido , Hígado , Ácido Oxálico , Animales , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Ratas , Antioxidantes/farmacología , Antioxidantes/química , Radicales Libres/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Ácido Oxálico/química , Ácido Oxálico/metabolismo , Ácido Oxálico/farmacología , Diamida/farmacología , Diamida/química , Estrés Oxidativo/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacosRESUMEN
In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca2+ release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1-10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca2+ channels responsible for the cardiac action potentials depolarization phase. Two types of Ca2+ currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca2+ currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.
Asunto(s)
Cardiotoxicidad , Insecticidas , Miocitos Cardíacos , ortoaminobenzoatos , Animales , Abejas/efectos de los fármacos , Abejas/fisiología , ortoaminobenzoatos/toxicidad , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Insecticidas/toxicidad , Cardiotoxicidad/etiología , Calcio/metabolismo , Contracción Miocárdica/efectos de los fármacos , Corazón/efectos de los fármacos , Corazón/fisiología , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Diamida/farmacologíaRESUMEN
In order to discover new meta-diamide compounds with good activity and novel structure, 15 related compounds were designed and synthesized by the bioisosterism principle with cyproflanilide as the lead compound. The insecticidal activities of these compounds against Plutella xylostella and Tetranychus cinnabarinus were tested, and the results of biological activity test showed that some compounds had more than 90 % insecticidal activity against Plutella xylostella at 1â mg/L and Tetranychus cinnabarinus at 100â mg/L. Especially, N-(2-bromo-6-(difluoromethoxy)-4-(perfluoro propan-2-yl)phenyl)-6-(isonicotinamido)picolinamide against Tetranychus cinnabarinus at 10â mg/L was 100 %, which was better than that of cyproflanilide. Molecular docking studies suggested that N-(2-bromo-6-(difluoromethoxy)-4-(perfluoropropan-2-yl)phenyl)-6-(4-cyano-2-methylbenzamido)picolinamide had a closely combined with the Plutella xylostella 3RHW (a glutamate-gated chloride channel). This study provides an avenue for designing and synthesizing a new generation of more effective pesticides.
Asunto(s)
Diseño de Fármacos , Insecticidas , Simulación del Acoplamiento Molecular , Mariposas Nocturnas , Piridinas , Tetranychidae , Insecticidas/síntesis química , Insecticidas/química , Insecticidas/farmacología , Animales , Piridinas/química , Piridinas/farmacología , Piridinas/síntesis química , Mariposas Nocturnas/efectos de los fármacos , Relación Estructura-Actividad , Tetranychidae/efectos de los fármacos , Diamida/farmacología , Diamida/química , Diamida/síntesis química , Estructura MolecularRESUMEN
Phthorimaea absoluta is an invasive solanaceous plant pest with highly devastating effects on tomato plant. Heavy reliance on insecticide use to tackle the pest has been linked to insecticide resistance selection in P. absoluta populations. To underline insights on P. absoluta insecticide resistance mechanisms to diamides and avermectins, we evaluated the transcriptomic profile of parental (field-collected) and F8 (lab-reared) populations. Furthermore, to screen for the presence of organophosphate and pyrethroid resistance, we assessed the gene expression levels of acetylcholinesterase (ace1) and para-type voltage-gated sodium channel (VGSG) genes in the F1 to F8 lab-reared progeny of diamide and avermectin exposed P. absoluta field-collected populations. The VGSG gene showed up-regulation in 12.5% and down-regulation in 87.5% of the screened populations, while ace1 gene showed up-regulation in 37.5% and down-regulation in 62.5% of the screened populations. Gene ontology of the differentially expressed genes from both parental and eighth generations of diamide-sprayed P. absoluta populations revealed three genes involved in the metabolic detoxification of diamides in P. absoluta. Therefore, our study showed that the detoxification enzymes found could be responsible for P. absoluta diamide-based resistance, while behavioural resistance, which is stimulus-dependent, could be attributed to P. absoluta avermectin resistance.
Asunto(s)
Insecticidas , Ivermectina/análogos & derivados , Lepidópteros , Mariposas Nocturnas , Animales , Lepidópteros/genética , Insecticidas/farmacología , Insecticidas/metabolismo , Mariposas Nocturnas/genética , Acetilcolinesterasa/metabolismo , Diamida , Perfilación de la Expresión Génica , LarvaRESUMEN
To increase the structural diversity of insecticides and meet the needs of effective integrated insect management, the structure of chlorantraniliprole was modified based on a previously established three-dimensional quantitative structure-activity relationship (3D-QSAR) model. The pyridinyl moiety in the structure of chlorantraniliprole was replaced with a 4-fluorophenyl group. Further modifications of this 4-fluorophenyl group by introducing a halogen atom at position 2 and an electron-withdrawing group (e.g., iodine, cyano, and trifluoromethyl) at position 5 led to 34 compounds with good insecticidal efficacy against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compound IV f against M. separata showed potency comparable to that of chlorantraniliprole. IV p against P. xylostella displayed a 4.5 times higher potency than chlorantraniliprole. In addition, IV d and chlorantraniliprole exhibited comparable potencies against S. frugiperda. Transcriptome analysis showed that the molecular target of compound IV f is the ryanodine receptor. Molecular docking was further performed to verify the mode of action and insecticidal activity against resistant P. xylostella.
Asunto(s)
Insecticidas , Mariposas Nocturnas , Animales , Insecticidas/farmacología , Insecticidas/química , Diamida/farmacología , Diamida/química , Simulación del Acoplamiento Molecular , Mariposas Nocturnas/metabolismo , ortoaminobenzoatos/farmacología , ortoaminobenzoatos/química , Relación Estructura-Actividad Cuantitativa , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Larva/metabolismoRESUMEN
The diamondback moth Plutella xylostella, a global insect pest of cruciferous vegetables, has evolved resistance to many classes of insecticides including diamides. Three point mutations (I4790M, I4790K, and G4946E) in the ryanodine receptor of P. xylostella (PxRyR) have been identified to associate with varying levels of resistance. In this study, we generated a knockin strain (I4790K-KI) of P. xylostella, using CRISPR/Cas9 to introduce the I4790K mutation into PxRyR of the susceptible IPP-S strain. Compared to IPP-S, the edited I4790K-KI strain exhibited high levels of resistance to both anthranilic diamides (chlorantraniliprole 1857-fold, cyantraniliprole 1433-fold) and the phthalic acid diamide flubendiamide (>2272-fold). Resistance to chlorantraniliprole in the I4790K-KI strain was inherited in an autosomal and recessive mode, and genetically linked with the I4790K knockin mutation. Computational modeling suggests the I4790K mutation reduces the binding of diamides to PxRyR by disrupting key hydrogen bonding interactions within the binding cavity. The approximate frequencies of the 4790M, 4790K, and 4946E alleles were assessed in ten geographical field populations of P. xylostella collected in China in 2021. The levels of chlorantraniliprole resistance (2.3- to 1444-fold) in these populations were significantly correlated with the frequencies (0.017-0.917) of the 4790K allele, but not with either 4790M (0-0.183) or 4946E (0.017-0.450) alleles. This demonstrates that the PxRyR I4790K mutation is currently the major contributing factor to chlorantraniliprole resistance in P. xylostella field populations within China. Our findings provide in vivo functional evidence for the causality of the I4790K mutation in PxRyR with high levels of diamide resistance in P. xylostella, and suggest that tracking the frequency of the I4790K allele is crucial for optimizing the monitoring and management of diamide resistance in this crop pest.
Asunto(s)
Diamida , Resistencia a los Insecticidas , Mariposas Nocturnas , Animales , Diamida/farmacología , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Insecticidas/metabolismo , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Mutación , ortoaminobenzoatos/farmacología , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismoRESUMEN
The meta-diamide (m-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m-diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, 1H NMR, 13C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds A-D exhibited 100% lethality against Plutella xylostella (P. xylostella) and Aphis craccivora Koch (A. craccivora) at 500 mg·L-1. Notably, for P. xylostella, compounds C-2, C-3, C-4 and D-2 demonstrated 60.00-100.00% insecticidal activity even at a concentration as low as 0.625 mg·L-1. As determined by structure-activity relationship (SAR) analysis, compounds with R1 = CH3 and R2 = Br (B-1, C-2 and D-2) and sulfoxide compound C-3 contained 100.00% lethality against A. craccivora at 500 mg·L-1, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound (C-3) requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing m-diamide compounds.
Asunto(s)
Benzamidas , Fluorocarburos , Insecticidas , Mariposas Nocturnas , Plaguicidas , Animales , Estructura Molecular , Diamida/química , Relación Estructura-Actividad , Insecticidas/farmacología , Insecticidas/química , SulfóxidosRESUMEN
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.
Asunto(s)
Insecticidas , Mariposas Nocturnas , ortoaminobenzoatos , Animales , Insecticidas/química , Diamida/farmacología , Diseño de Fármacos , Relación Estructura-Actividad , Estructura MolecularRESUMEN
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 (â SUS × â PR) × and an incompletely dominant trait for H2 (â 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.
Asunto(s)
Fluorocarburos , Insecticidas , Mariposas Nocturnas , Ftalimidas , Pirazoles , Sulfonas , ortoaminobenzoatos , Humanos , Animales , Spodoptera/genética , Diamida/farmacología , Puerto Rico , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , LarvaRESUMEN
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.
Asunto(s)
Leucotrieno B4 , Neutrófilos , Salmonella typhimurium , Acetilcisteína/farmacología , Diamida/farmacología , Leucotrienos/farmacología , Factores Quimiotácticos , Oxidación-Reducción , Antioxidantes/farmacología , Glutatión/farmacología , Compuestos de Sulfhidrilo/farmacologíaRESUMEN
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.
Asunto(s)
Insecticidas , MicroARNs , Animales , Spodoptera/genética , MicroARNs/genética , Diamida/farmacología , Insecticidas/farmacología , Regulación de la Expresión Génica , Resistencia a los Insecticidas/genética , LarvaRESUMEN
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.
Asunto(s)
Insecticidas , Líquidos Iónicos , Impresión Molecular , Pirazoles , ortoaminobenzoatos , Agua , Polímeros Impresos Molecularmente , Diamida , Impresión Molecular/métodos , Cromatografía Líquida de Alta Presión , Polímeros , Adsorción , Fenómenos Magnéticos , Extracción en Fase Sólida/métodosRESUMEN
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.
Asunto(s)
Insecticidas , Nanotubos de Carbono , Cromatografía Liquida , Cromatografía Líquida de Alta Presión/métodos , Verduras/química , Diamida , Espectrometría de Masas en Tándem/métodos , Nanotubos de Carbono/química , Cromatografía Líquida con Espectrometría de Masas , Extracción en Fase Sólida/métodos , Límite de DetecciónRESUMEN
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.
Asunto(s)
Insecticidas , Oryza , Contaminantes Químicos del Agua , Animales , Insecticidas/toxicidad , Ecosistema , Zooplancton , Diamida/farmacología , Organismos Acuáticos , Contaminantes Químicos del Agua/toxicidadRESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 2 , Ratones , Ratas , Animales , Proteínas Quinasas Activadas por AMP , Diamida , Glucosa , Piridinas/farmacología , Piperidinas , AmidasRESUMEN
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.
Asunto(s)
Abejas , Escarabajos , Insecticidas , ortoaminobenzoatos , Animales , Abejas/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Escarabajos/efectos de los fármacos , Diamida , Himenópteros/efectos de los fármacos , Insecticidas/farmacología , ortoaminobenzoatos/farmacologíaRESUMEN
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.
Asunto(s)
Insecticidas , Mariposas Nocturnas , Animales , Humanos , Diamida/farmacología , Simulación del Acoplamiento Molecular , Células HEK293 , Mariposas Nocturnas/genética , Spodoptera/metabolismo , Insecticidas/farmacología , Insecticidas/química , ortoaminobenzoatos/farmacología , ortoaminobenzoatos/química , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Resistencia a los Insecticidas/genéticaRESUMEN
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.