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1.
Rapid Commun Mass Spectrom ; 38(9): e9729, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38456250

RESUMO

RATIONALE: Ensuring the global safety and effectiveness of agrochemicals has become imperative. An in-depth understanding of impurity profiles of products is crucial, especially for high-demand agrochemicals, where impurities may be more toxic and persistent than original agrochemicals. This study focuses on the detection and identification of impurities in a commercial chlorantraniliprole (CAP), an anthranilic diamide class broad-spectrum insecticide. METHODS: Commercial CAP was collected from an agrochemical supplier in India and was analyzed using a high-performance liquid chromatography-photodiode array (HPLC-PDA) (Agilent 1260; wavelength, 220 nm) with a Zorbax RP SB-C18 (250 × 4.6 mm, 5 µm) column and liquid chromatography-mass spectrometry (LC-MS) (Agilent 6545 quadrupole time of flight (Q-TOF)) techniques to identify the impurities. The impurities were isolated by preparative HPLC using a Zorbax-DB C18 (250 × 9.4 mm, 5 µm) column. liquid chromatography- tandem mass spectrometry (LC-MS/MS) experiments (Q-TOF) were performed on CAP and its impurities to obtain their structural data. RESULTS: HPLC-PDA analysis of CAP showed four major impurities (IM-1 to IM-4) ranging from 0.76% to 4.1%. The positive ion electrospray ionization (ESI) mass spectra of CAP and its impurities showed dominant [M + H]+ ions in addition to [M + Na]+ , [M + K]+ , and [2M + Na]+ ions. High-resolution mass spectrometry (HRMS) data provided the elemental composition of the compounds, and isotopic distribution patterns revealed the number of Cl and/or Br atoms present in them. The structures of impurities were proposed based on the LC-MS/MS) data and further confirmed by nuclear magnetic resonance (NMR) data on isolated impurities/synthesis. CONCLUSION: The quality and impurities of CAP, a popular insecticide, must be assessed and described for its efficacy and safety. In this study, four impurities of CAP were detected using HPLC and successfully characterized using LC-HRMS, LC-MS/MS, and NMR data. The method is useful for verifying the purity of CAP as well as helping in the identification of its possible impurities.


Assuntos
Inseticidas , ortoaminobenzoatos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Íons
3.
J Agric Food Chem ; 72(7): 3363-3373, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38324778

RESUMO

Cyantraniliprole is a novel insecticide recently introduced for rice pest control that may cause potential threats to the red swamp crayfish (Procambarus clarkii) in rice-crayfish coculture systems. In this study, we investigated the acute toxicity of cyantraniliprole against P. clarkii with a LC50 value of 149.77 mg/L (96 h), first. Some abnormal behaviors of P. clarkii treated with 125 mg/L cyantraniliprole, including incunabular hyperexcitability, imbalance, inactivity, and increased excretion were observed. Moreover, it was observed that exposure to 5 mg/L cyantraniliprole for 14 days resulted in histopathological alterations in abdominal muscle, gills, hepatopancreas, and intestines. Furthermore, exposure to 0.05 and 5 mg/L cyantraniliprole induced increased activities of several oxidative stress-related enzymes, which was verified by the upregulation of related genes. Additionally, dysregulation of the intestinal microbiota was determined via 16S rRNA sequencing. These results will provide the basis for the utilization of cyantraniliprole in the fields of rice-crayfish integrated system.


Assuntos
Microbioma Gastrointestinal , Oryza , Pirazóis , ortoaminobenzoatos , Animais , Astacoidea/genética , RNA Ribossômico 16S , Estresse Oxidativo
4.
J Agric Food Chem ; 72(7): 3406-3414, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38329423

RESUMO

The expression of P450 genes is regulated by trans-regulatory factors or cis-regulatory elements and influences how endogenous or xenobiotic substances are metabolized in an organism's tissues. In this study, we showed that overexpression of the cytochrome P450 gene, CYP6CY22, led to resistance to cyantraniliprole in Aphis gossypii. The expression of CYP6CY22 increased in the midgut and remaining carcass of the CyR strain, and after repressing the expression of CYP6CY22, the mortality of cotton aphids increased 2.08-fold after exposure to cyantraniliprole. Drosophila ectopically expressing CYP6CY22 exhibited tolerance to cyantraniliprole and cross-tolerance to xanthotoxin, quercetin, 2-tridecanone, tannic acid, and nicotine. Moreover, transcription factor CF2-II (XM_027994540.2) is transcribed only as the splicing variant isoform CF2-II-AS, which was found to be 504 nucleotides shorter than CF2-II in A. gossypii. RNAi and yeast one-hybrid (Y1H) results indicated that CF2-II-AS positively regulates CYP6CY22 and binds to cis-acting element p (-851/-842) of CYP6CY22 to regulate its overexpression. The above results indicated that CYP6CY22 was regulated by the splicing isoform CF2-II-AS, which will help us further understand the mechanism of transcriptional adaption of cross-tolerance between synthetic insecticides and plant secondary metabolites mediated by P450s.


Assuntos
Afídeos , Inseticidas , Polifenóis , Pirazóis , ortoaminobenzoatos , Animais , Processamento Alternativo , Afídeos/genética , Afídeos/metabolismo , Xenobióticos/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Isoformas de Proteínas/genética , Inseticidas/farmacologia , Inseticidas/metabolismo , Resistência a Inseticidas/genética
5.
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
6.
Adv Wound Care (New Rochelle) ; 13(4): 155-166, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38299969

RESUMO

Objective: Given the significant economic, health care, and personal burden of acute and chronic wounds, we investigated the dose dependent wound healing mechanisms of two Avena sativa derived compounds: avenanthramide (AVN) and ß-Glucan. Approach: We utilized a splinted excisional wound model that mimics human-like wound healing and performed subcutaneous AVN and ß-Glucan injections in 15-week-old C57BL/6 mice. Histologic and immunohistochemical analysis was performed on the explanted scar tissue to assess changes in collagen architecture and cellular responses. Results: AVN and ß-Glucan treatment provided therapeutic benefits at a 1% dose by weight in a phosphate-buffered saline vehicle, including accelerated healing time, beneficial cellular recruitment, and improved tissue architecture of healed scars. One percent AVN treatment promoted an extracellular matrix (ECM) architecture similar to unwounded skin, with shorter, more randomly aligned collagen fibers and reduced inflammatory cell presence in the healed tissue. One percent ß-Glucan treatment promoted a tissue architecture characterized by long, thick bundles of collagen with increased blood vessel density. Innovation: AVN and ß-Glucan have previously shown promise in promoting wound healing, although the therapeutic efficacies and mechanisms of these bioactive compounds remain incompletely understood. Furthermore, the healed ECM architecture of these wounds has not been characterized. Conclusions: AVN and ß-Glucan accelerated wound closure compared to controls through distinct mechanisms. AVN-treated scars displayed a more regenerative tissue architecture with reduced inflammatory cell recruitment, while ß-Glucan demonstrated increased angiogenesis with more highly aligned tissue architecture more indicative of fibrosis. A deeper understanding of the mechanisms driving healing in these two naturally derived therapeutics will be important for translation to human use.


Assuntos
Cicatriz , beta-Glucanas , ortoaminobenzoatos , Animais , Camundongos , beta-Glucanas/farmacologia , Colágeno , Camundongos Endogâmicos C57BL , Cicatrização
7.
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
8.
Appl Environ Microbiol ; 90(2): e0124723, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38289097

RESUMO

To elucidate why plasmid-borne catabolic ability differs among host bacteria, we assessed the expression dynamics of the Pant promoter on the carbazole-degradative conjugative plasmid pCAR1 in Pseudomonas putida KT2440(pCAR1) (hereafter, KTPC) and Pseudomonas resinovorans CA10. The Pant promoter regulates the transcription of both the car and ant operons, which are responsible for converting carbazole into anthranilate and anthranilate into catechol, respectively. In the presence of anthranilate, transcription of the Pant promoter is induced by the AraC/XylS family regulator AntR, encoded on pCAR1. A reporter cassette containing the Pant promoter followed by gfp was inserted into the chromosomes of KTPC and CA10. After adding anthranilate, GFP expression in the population of CA10 showed an unimodal distribution, whereas a small population with low GFP fluorescence intensity appeared for KTPC. CA10 has a gene, antRCA, that encodes an iso-functional homolog of AntR on its chromosome. When antRCA was disrupted, a small population with low GFP fluorescence intensity appeared. In contrast, overexpression of pCAR1-encoded AntR in KTPC resulted in unimodal expression under the Pant promoter. These results suggest that the expression of pCAR1-encoded AntR is insufficient to ameliorate the stochastic expression of the Pant promoter. Raman spectra of single cells collected using deuterium-labeled carbazole showed that the C-D Raman signal exhibited greater variability for KTPC than CA10. These results indicate that heterogeneity at the transcriptional level of the Pant promoter due to insufficient AntR availability causes fluctuations in the pCAR1-borne carbazole-degrading capacity of host bacterial cells.IMPORTANCEHorizontally acquired genes increase the competitiveness of host bacteria under selective conditions, although unregulated expression of foreign genes may impose fitness costs. The "appropriate" host for a plasmid is empirically known to maximize the expression of plasmid-borne traits. In the case of pCAR1-harboring Pseudomonas strains, P. resinovorans CA10 exhibits strong carbazole-degrading capacity, whereas P. putida KT2440 harboring pCAR1 exhibits low degradation capacity. Our results suggest that a chromosomally encoded transcription factor affects transcriptional and metabolic fluctuations in host cells, resulting in different carbazole-degrading capacities as a population. This study may provide a clue for determining appropriate hosts for a plasmid and for regulating the expression of plasmid-borne traits, such as the degradation of xenobiotics and antibiotic resistance.


Assuntos
Pseudomonas putida , Plasmídeos/genética , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Regiões Promotoras Genéticas , Carbazóis/metabolismo , ortoaminobenzoatos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
9.
Sci Rep ; 14(1): 2406, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38286866

RESUMO

A field study was conducted to investigate the persistence of foliar-applied thiamethoxam 25% WG at a rate of 25 g ai ha-1 and chlorantraniliprole 18.5% SC at 30 g ai ha-1 in various parts of rice plants, including whole grain rice, brown rice, bran, husk, straw, and cooked rice. Liquid Chromatography-Mass spectrometry/Mass spectrometry was used for sample analysis. Chlorantraniliprole residues were found to persist in whole grains, bran, husk, and straw at the time of harvest, while thiamethoxam residue was not detected in harvested grains, processed products, or straw. The study concluded that foliar-applied chlorantraniliprole and thiamethoxam did not pose any dietary risk in cooked rice. In a pre-storage seed treatment study, thiamethoxam 30% FS at 3 mL kg-1 was evaluated against Angoumois grain moth infestation during storage. The seeds remained unharmed for nine months and exhibited significantly less moth damage (2.0%) even after twelve months of storage. Thiamethoxam residues persisted for more than one year in whole rice grain, brown rice, bran, and husk with seed treatment, with higher residue levels observed in bran and husk. Parboiling and cooking led to the degradation of thiamethoxam residues.


Assuntos
Inseticidas , Oryza , ortoaminobenzoatos , Inseticidas/metabolismo , Tiametoxam/metabolismo , Oryza/metabolismo , Sementes/química
10.
Bioengineered ; 15(1): 2305029, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38258524

RESUMO

Oats (Avena sativa L.) are one of the worldwide cereal crops. Avenanthramides (AVNs), the unique plant alkaloids of secondary metabolites found in oats, are nutritionally important for humans and animals. Numerous bioactivities of AVNs have been investigated and demonstrated in vivo and in vitro. Despite all these, researchers from all over the world are taking efforts to learn more knowledge about AVNs. In this work, we highlighted the recent updated findings that have increased our understanding of AVNs bioactivity, distribution, and especially the AVNs biosynthesis. Since the limits content of AVNs in oats strictly hinders the demand, understanding the mechanisms underlying AVN biosynthesis is important not only for developing a renewable, sustainable, and environmentally friendly source in both plants and microorganisms but also for designing effective strategies for enhancing their production via induction and metabolic engineering. Future directions for improving AVN production in native producers and heterologous systems for food and feed use are also discussed. This summary will provide a broad view of these specific natural products from oats.


• Avenanthramides are unique nutritional alkaloids in oats• AVN bioactivity, distribution, and the potential AVNs biosynthesis are discussed• AVNs can be produced via induction and metabolic engineering.


Assuntos
Avena , Grão Comestível , Animais , Humanos , ortoaminobenzoatos , Amidas , Fenóis
11.
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
12.
Pest Manag Sci ; 80(3): 1107-1117, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37862262

RESUMO

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.


Assuntos
Glutationa Transferase , Mariposas , ortoaminobenzoatos , Animais , Mariposas/genética , Larva , Glutationa
13.
J Biochem Mol Toxicol ; 38(1): e23521, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37706603

RESUMO

N-substitued anthranilic acid derivatives are commonly found in the structure of many biologically active molecules. In this study, new members of hydrazones derived from anthranilic acid (1-15) were synthesized and investigated their effect on some metabolic enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly). Results indicated that all the molecules exhibited potent inhibitory effects against all targets as compared to the standard inhibitors, revealed by IC50 values. Ki values of compounds for AChE, BChE, and α-Gly enzymes were obtained in the ranges 66.36 ± 8.30-153.82 ± 13.41, 52.68 ± 6.38-113.86, and 2.13 ± 0.25-2.84 nM, respectively. The molecular docking study was performed for the most active compounds to the determination of ligand-enzyme interactions. Binding affinities of the most active compound were found at the range of -9.70 to -9.00 kcal/mol for AChE, -11.60 to -10.60 kcal/mol for BChE, and -10.30 to -9.30 kcal/mol for α-Gly. Molecular docking simulations showed that the novel compounds had preferential interaction with AChE, BChE, and α-Gly. Drug-likeness properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyzes of all synthesized compounds (1-15) were estimated and their toxic properties were evaluated as well as their therapeutic properties. Moreover, molecular dynamics simulations were carried out to understand the accuracy of the most potent derivatives of docking studies.


Assuntos
Acetilcolinesterase , Butirilcolinesterase , ortoaminobenzoatos , Butirilcolinesterase/química , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Simulação de Acoplamento Molecular , Hidrazonas/farmacologia , Relação Estrutura-Atividade , Glicosídeo Hidrolases/metabolismo , Estrutura Molecular
14.
Pest Manag Sci ; 80(3): 988-995, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37822111

RESUMO

BACKGROUND: The bites and blood sucking of bed bugs (Cimex spp.) (Hemiptera: Cimicidae) pose a serious threat to human physical and mental health. Application of an effective repellent can prevent or reduce bed bug bites. Previous studies on repellent screening mainly focused on Cimex lectularius L. In this study, we investigated the repellent effect of two safe food additives, ethyl anthranilate (EA) and butyl anthranilate (BA), against Cimex hemipterus (F.), and also explored the role of antennae and mouthparts on C. hemipterus perception of repellents. RESULTS: Both EA and BA had a strong repellent effect against tropical bed bugs and their repellency was similar or lower than that of N,N-diethyl-3-methyl benzoyl amide, depending on whether or not a CO2 source was present. EA had higher repellency than BA and exhibited repellency to C. hemipterus for 3 days when a CO2 source was present. C. hemipterus avoided resting on 20% EA- and BA-treated harborages. Applying 20% EA and BA on rabbit skin significantly reduced the blood intake of C. hemipterus within 2 h. C. hemipterus could perceive EA and BA after their antennae or mouthparts or both antennae and mouthparts were removed. CONCLUSION: Both EA and BA had strong repellency against C. hemipterus, with EA being more repellent. Ablation of antennae and mouthparts did not affect the perception of EA and BA by C. hemipterus. © 2023 Society of Chemical Industry.


Assuntos
Percevejos-de-Cama , Repelentes de Insetos , Animais , Humanos , Coelhos , Dióxido de Carbono/farmacologia , Repelentes de Insetos/farmacologia , ortoaminobenzoatos/farmacologia
15.
Sci Total Environ ; 912: 169229, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38072259

RESUMO

The anthranilic diamide insecticide chlorantraniliprole has been extensively applied to control Lepidoptera pests. However, its overuse leads to the development of resistance and accumulation of residue in the environment. Four P450s (CYP6CV5, CYP9A68, CYP321F3, and CYP324A12) were first found to be constitutively overexpressed in an SSB CAP-resistant strain. It is imperative to further elucidate the molecular mechanisms underlying P450s-mediated CAP resistance for mitigating its environmental contamination. Here, we heterologously expressed these four P450s in insect cells and evaluated their abilities to metabolize CAP. Western blotting and reduced CO difference spectrum tests showed that these four P450 proteins had been successfully expressed in Sf9 cells, which are indicative of active functional enzymes. The recombinant proteins CYP6CV5, CYP9A68, CYP321F3, and CYP324A12 exhibited a preference for metabolizing the fluorescent P450 model probe substrates EC, BFC, EFC, and EC with enzyme activities of 0.54, 0.67, 0.57, and 0.46 pmol/min/pmol P450, respectively. In vitro metabolism revealed distinct CAP metabolic rates (0.97, 0.86, 0.75, and 0.55 pmol/min/pmol P450) and efficiencies (0.45, 0.37, 0.30, and 0.17) of the four recombinant P450 enzymes, thereby elucidating different protein catalytic activities. Furthermore, molecular model docking confirmed metabolic differences and efficiencies of these P450s and unveiled the hydroxylation reaction in generating N-demethylation and methylphenyl hydroxylation during CAP metabolism. Our findings not only first provide new insights into the mechanisms of P450s-mediated metabolic resistance to CAP at the protein level in SSB but also demonstrate significant differences in the capacities of multiple P450s for insecticide degradation and facilitate the evaluation and mitigation of toxic risks associated with CAP application in the environment.


Assuntos
Inseticidas , Lepidópteros , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , ortoaminobenzoatos
16.
Chem Biodivers ; 21(2): e202301602, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38102075

RESUMO

Compound 3, a trimeric anthranilic acid peptide, and another three metabolites were isolated from an organic extract from the culture medium of Malbranchea flocciformis ATCC 34530. The chemical structure proposed previously for 3 was unequivocally assigned via synthesis and X-ray diffraction analysis. Tripeptide 3 showed insulinotropic properties by decreasing the postprandial peak in healthy and hyperglycemic mice. It also increased glucose-induced insulin secretion in INS-1E at 5 µM, specifically at higher glucose concentrations. These results revealed that 3 might act as an insulin sensitizer and a non-classical insulin secretagogue. Altogether, these findings are in harmony with the in vivo oral glucose tolerance test and acute oral hypoglycemic assay. Finally, the chemical composition of the extract was established by the Global Natural Products Social Molecular Network platform. Phylogenetic analysis using the internal transcribed spacer region revealed that M. flocciformis ATCC 34530 is related to the Malbrancheaceae.


Assuntos
Hipoglicemiantes , Insulina , Onygenales , ortoaminobenzoatos , Camundongos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Filogenia , Insulina/metabolismo , Glucose
17.
Cell Calcium ; 117: 102840, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38160478

RESUMO

Atrial fibrillation (AF) is common in pulmonary hypertension (PH), whereas the mechanisms and treatments remain to be explored. TRPV2 regulates the structure and function of the cardiovascular system; however, little attention has been given to its role in AF. This study was to determine whether TRPV2 was involved in PH-induced AF and the effects of TRPV2 inhibitor tranilast on AF in rat models of PH. Monocrotaline (MCT) and SU5416/hypoxia (SuHx)-induced PH models were performed to detect atrial electrophysiological parameters. Daily tranilast (a TRPV2 inhibitor) or saline was given starting 1 day before PH establishment. PH increased the susceptibility to AF, with TRPV2 up-regulated in the right atria. Compared to PH rats, tranilast reduced AF inducibility and the prolongations of ERP and APD; mitigated cardiopulmonary remodeling and the increases in P-wave duration and P-R interval; partially reversed the down-regulation of ion channels such as Cav1.2, Nav1.5, Kv4.3, Kv4.2, Kv1.5, Kir2.1, Kir3.1, Kir3.4 as well as connexin (Cx) 40 and Cx43; improved right atrial (RA) fibrosis, enlargement, and myocardial hypertrophy; decreased the accumulation of inflammatory cells; down-regulated inflammatory indicators such as TNF-α, IL-1ß, CXCL1, and CXCL2; and inhibited the activation of the PI3K-AKT-NF-κB signaling pathway. Our results reveal that TRPV2 participates in PH-induced AF, and TRPV2 inhibitor tranilast prevents PH-induced RA remodeling. TRPV2 might be a promising target for PH-induced AF.


Assuntos
Fibrilação Atrial , Hipertensão Pulmonar , ortoaminobenzoatos , Ratos , Animais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Átrios do Coração/metabolismo , Modelos Animais de Doenças
18.
Aquat Toxicol ; 267: 106812, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38150864

RESUMO

Predaceous diving beetles (dytiscids) are important top insect predators in various natural, agricultural, and artificial water bodies. How they respond to human disturbances such as insecticide contamination to their habitats has been understudied. In this study, we investigated the lethal effects of lambda-cyhalothrin, chlorantraniliprole, and thiamethoxam at nominal field concentrations in 3 cm-deep water in a hypothetical paddy field (Ci,3) on adult Dytiscus sinensis Feng (Coleoptera: Dytiscidae). Lambda-cyhalothrin exhibited significant lethal effects on D. sinensis adults with its Ci,3 exceeding the 95 % confidence interval lower limits for 24, 48, 72, and 96 h- LC99. Chlorantraniliprole and thiamethoxam showed no significant lethal effects on D. sinensis adults at their respective Ci,3 at 24, 48, or 72 h. Additionally, we assessed the temporal propensity of D. sinensis adults to exit water contaminated with chlorantraniliprole and thiamethoxam, respectively. There were significantly more individuals that temporally exited the chlorantraniliprole-contaminated water than clean water 30 min after placing a tile island in the test arena. Meanwhile, thiamethoxam-contaminated water did not repel significantly more individuals than clean water when observed at 10, 30, or 60 min. The study highlights the availability and importance of selecting safer insecticides for dytiscid conservation in agricultural and adjacent habitats, considering the potential of these water bodies becoming ecological traps that keep attracting and killing aquatic beneficials. The water-exiting behavior found indicates the capability of some wildlife to effectively avoid further exposure to toxicants.


Assuntos
Besouros , Inseticidas , Nitrilas , Piretrinas , Poluentes Químicos da Água , ortoaminobenzoatos , Animais , Humanos , Tiametoxam/farmacologia , Besouros/fisiologia , Água/farmacologia , Neonicotinoides/toxicidade , Poluentes Químicos da Água/toxicidade , Inseticidas/toxicidade
19.
J Biol Chem ; 300(1): 105565, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103642

RESUMO

The biochemical SRX (super-relaxed) state of myosin has been defined as a low ATPase activity state. This state can conserve energy when the myosin is not recruited for muscle contraction. The SRX state has been correlated with a structurally defined ordered (versus disordered) state of muscle thick filaments. The two states may be linked via a common interacting head motif (IHM) where the two heads of heavy meromyosin (HMM), or myosin, fold back onto each other and form additional contacts with S2 and the thick filament. Experimental observations of the SRX, IHM, and the ordered form of thick filaments, however, do not always agree, and result in a series of unresolved paradoxes. To address these paradoxes, we have reexamined the biochemical measurements of the SRX state for porcine cardiac HMM. In our hands, the commonly employed mantATP displacement assay was unable to quantify the population of the SRX state with all data fitting very well by a single exponential. We further show that mavacamten inhibits the basal ATPases of both porcine ventricle HMM and S1 (Ki, 0.32 and 1.76 µM respectively) while dATP activates HMM cooperatively without any evidence of an SRX state. A combination of our experimental observations and theories suggests that the displacement of mantATP in purified proteins is not a reliable assay to quantify the SRX population. This means that while the structurally defined IHM and ordered thick filaments clearly exist, great care must be employed when using the mantATP displacement assay.


Assuntos
Trifosfato de Adenosina , Ensaios Enzimáticos , Miosina não Muscular Tipo IIA , Suínos , ortoaminobenzoatos , Animais , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/metabolismo , Motivos de Aminoácidos , Benzilaminas/farmacologia , Ensaios Enzimáticos/métodos , Ensaios Enzimáticos/normas , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/enzimologia , Ventrículos do Coração/metabolismo , Contração Miocárdica , Subfragmentos de Miosina/química , Subfragmentos de Miosina/metabolismo , Miosina não Muscular Tipo IIA/química , Miosina não Muscular Tipo IIA/metabolismo , ortoaminobenzoatos/metabolismo , Uracila/análogos & derivados , Uracila/farmacologia
20.
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
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