Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.484
Filtrar
2.
ACS Sens ; 8(1): 19-27, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36602887

RESUMO

A major limitation of time-lapse microscopy combined with fluorescent biosensors, a powerful tool for quantifying spatiotemporal dynamics of signaling in single living cells, is low-experimental throughput. To overcome this limitation, we created a highly customizable, MATLAB-based platform: flexible automated liquid-handling combined microscope (FALCOscope) that coordinates an OpenTrons liquid handler and a fluorescence microscope to automate drug treatments, fluorescence imaging, and single-cell analysis. To test the feasibility of the FALCOscope, we quantified G protein-coupled receptor (GPCR)-stimulated Protein Kinase A activity and cAMP responses to GPCR agonists and antagonists. We also characterized cAMP dynamics induced by GPR68/OGR1, a proton-sensing GPCR, in response to variable extracellular pH values. GPR68-induced cAMP responses were more transient in acidic than neutral pH values, suggesting a pH-dependence for signal attenuation. Ogerin, a GPR68 positive allosteric modulator, enhanced cAMP response most strongly at pH 7.0 and sustained cAMP response for acidic pH values, thereby demonstrating the capability of the FALCOscope to capture allosteric modulation. At a high concentration, ogerin increased cAMP signaling independent of GPR68, likely via phosphodiesterase inhibition. The FALCOscope system thus enables enhanced throughput single-cell dynamic measurements and is a versatile system for interrogating spatiotemporal regulation of signaling molecules in living cells and for drug profiling and screening.


Assuntos
Álcoois Benzílicos , Transdução de Sinais , Álcoois Benzílicos/farmacologia , Triazinas , Microscopia de Fluorescência
3.
PLoS Comput Biol ; 19(1): e1010797, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36608108

RESUMO

To aid understanding of the effect of antiviral treatment on population-level influenza transmission, we used a novel pharmacokinetic-viral kinetic transmission model to test the correlation between nasal viral load and infectiousness, and to evaluate the impact that timing of treatment with the antivirals oseltamivir or baloxavir has on influenza transmission. The model was run under three candidate profiles whereby infectiousness was assumed to be proportional to viral titer on a natural-scale, log-scale, or dose-response model. Viral kinetic profiles in the presence and absence of antiviral treatment were compared for each individual (N = 1000 simulated individuals); subsequently, viral transmission mitigation was calculated. The predicted transmission mitigation was greater with earlier administration of antiviral treatment, and with baloxavir versus oseltamivir. When treatment was initiated 12-24 hours post symptom onset, the predicted transmission mitigation was 39.9-56.4% for baloxavir and 26.6-38.3% for oseltamivir depending on the infectiousness profile. When treatment was initiated 36-48 hours post symptom onset, the predicted transmission mitigation decreased to 0.8-28.3% for baloxavir and 0.8-19.9% for oseltamivir. Model estimates were compared with clinical data from the BLOCKSTONE post-exposure prophylaxis study, which indicated the log-scale model for infectiousness best fit the observed data and that baloxavir affords greater reductions in secondary case rates compared with neuraminidase inhibitors. These findings suggest a role for baloxavir and oseltamivir in reducing influenza transmission when treatment is initiated within 48 hours of symptom onset in the index patient.


Assuntos
Influenza Humana , Tiepinas , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Oxazinas/farmacologia , Oxazinas/uso terapêutico , Piridinas/farmacologia , Tiepinas/farmacologia , Tiepinas/uso terapêutico , Triazinas/farmacologia
5.
Chemosphere ; 315: 137731, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608878

RESUMO

Flumequine (FLU) and nadifloxacin (NAD), as emerging contaminants, have received extensive attention recently. In this study, a triazine-based microporous organic network (TMON) was synthetized and developed as an excellent adsorbent for FLU and NAD. The adsorption behavior and influence factors were investigated in both single and binary systems. Insight into the adsorption mechanisms were conducted through experiments, models, and computational studies, from macro and micro perspectives including functional groups, adsorption sites, adsorption energy and frontier molecular orbital. The results showed that the maximum adsorption capacities of TMON for FLU and NAD are 325.27 and 302.28 mg/g under 30 °C higher than records reported before. TMON exhibits the better adaptability and anti-interference ability for influence factors, leading to the preferable application effect in kinds of real water samples. TMON also shows the application potentials for the adsorption of other quinolone antibiotics and CO2 capture. Hydrogen-bonding interaction played the most critical role compared to π-π stacking effect, π-π electron-donor-acceptor interaction, CH-π interaction, and hydrophobic interaction during the adsorption. TMON could be regarded as a promising environmental adsorbent for its large surface area, stable physical and chemical properties, excellent recyclability, and wide range of applications.


Assuntos
Triazinas , Poluentes Químicos da Água , Adsorção , NAD , Poluentes Químicos da Água/análise
6.
J Hazard Mater ; 446: 130708, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36608577

RESUMO

Demethylthio is one of the most important ways for microorganisms to metabolize triazine herbicides. Previous studies have found that the initial reaction of prometryn catabolism in Leucobacter triazinivorans JW-1 was the hydroxylation of its methylthio group, however, the corresponding functional enzyme was not yet clear. In this study, the gene proA was responsible for the initial step of prometryn catabolism from the strain JW-1 was cloned and expressed, and the purified amidohydrolases ProA have the ability to transform prometryn to 2-hydroxypropazine and methanethiol. The optimized reaction temperature and pH of ProA were 45 °C and 7.0, respectively, and the kinetic constants Km and Vmax of ProA for the catalysis of prometryn were 32.6 µM and 0.09 µmol/min/mg, respectively. Molecular docking analyses revealed that different catalysis efficiency of ProA and TrzN (Nocardioides sp. C190) for prometryn and atrazine was due to non-covalent changes in amino acid residues. Our findings provide new insights into the understanding of s-triazine catabolism at the molecular level.


Assuntos
Herbicidas , Prometrina , Prometrina/metabolismo , Triazinas/metabolismo , Simulação de Acoplamento Molecular , Herbicidas/metabolismo , Amidoidrolases , Catálise , Nocardioides/metabolismo
7.
Eur J Med Chem ; 248: 115117, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36657300

RESUMO

Yellow fever disease is one of public health concerns in the tropics. Despite its significant medicinal and economic impact among large groups of the population, there is a lack of effective treatment against yellow fever. In this regard, here we describe the synthesis of a series of new 6-aryl-3-R-amino-1,2,4-triazin-5(4H)-ones and evaluation of their in vitro inhibitory activity against yellow fever virus. Among all tested compounds 4 derivatives possessing strong inhibitory activity at µM concentrations were identified. All the active compounds revealed a good toxicity profile. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment of yellow fever virus infection in vivo.


Assuntos
Triazinas , Vírus da Febre Amarela , Triazinas/farmacologia , Antivirais/farmacologia
8.
J Enzyme Inhib Med Chem ; 38(1): 2157411, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36629449

RESUMO

Mutant isocitrate dehydrogenase (IDH) 2 "IDH2m" acquires a neo-enzymatic activity reducing α-ketoglutarate to an oncometabolite, D-2-hydroxyglutarate (2-HG). Three s-triazine series were designed and synthesised using enasidenib as a lead compound. In vitro anticancer screening via National Cancer Institute "NCI" revealed that analogues 6a, 6c, 6d, 7g, and 7l were most potent, with mean growth inhibition percentage "GI%" = 66.07, 66.00, 53.70, 35.10, and 81.15, respectively, followed by five-dose screening. Compounds 6c, 6e, and 7c were established as the best IDH2R140Q inhibitors compared to enasidenib, reporting IC50 = 101.70, 67.01, 88.93, and 75.51 nM, respectively. More importantly, 6c, 6e, and 7c displayed poor activity against the wild-type IDH2, IC50 = 2928, 2295, and 3128 nM, respectively, which implementing high selectivity and accordingly safety. Furthermore, 6c was screened for cell cycle arrest, apoptosis induction, and western blot analysis. Finally, computational tools were applied to predict physicochemical properties and binding poses in IDH2R140Q allosteric site.


Assuntos
Antineoplásicos , Isocitrato Desidrogenase , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Mutação , Antineoplásicos/farmacologia , Triazinas/farmacologia , Triazinas/química
9.
Bioorg Med Chem ; 78: 117133, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36599263

RESUMO

In this article, we designed and synthesized a series of novel thiophene-triazine derivatives bearing arylurea unit as potent dual PI3K/mTOR inhibitors. The cytotoxicity of all the target compounds were evaluated against nine cancer cell lines (breast cancer cell line MCF-7, lung cancer cell lines A549, NCI-H460, H2228 and H1975, cervical cancer cell lines Hela and Hela-MDR, ovarian cancer cell lines Ovcar-2 and glioma U87MG) and the kinase inhibitory activity against PI3K/mTOR kinases was also tested. The results demonstrated that most of the target compounds exhibited moderate to excellent activity and high selectivity against one or more cancer cell lines. Among them, seven compounds displayed better activity than lead compound GDC-0941. The inhibitory activity of the most promising compound on nine cancer cell lines was 302.5 times better than that of GDC-0941 with the IC50 values as low as 0.008 ± 0.002 µM, and the inhibitory activity against PI3Kα and mTOR kinase was excellent, with the IC50 values of 177.41 and 12.24 nM, respectively, indicating that it was a potential dual PI3Kα/mTOR inhibitor. The Structure-Activity Relationships (SARs) indicated that the introduction of the arylurea group significantly improved the cellular and kinase activities of the target compounds. Moreover, the results of toxicity and hemolysis experiments demonstrated that the most promising compound had low toxicity and good safety. The results of PCR assay and molecular docking modes showed that it was a potential PI3K/mTOR inhibitor, which was worthy of further study.


Assuntos
Antineoplásicos , Fosfatidilinositol 3-Quinases , Humanos , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Serina-Treonina Quinases TOR , Triazinas/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais
10.
Eur J Med Chem ; 247: 115035, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36603507

RESUMO

Influenza is one of the leading causes of disease-related mortalities worldwide. Several strategies have been implemented during the past decades to hinder the replication cycle of influenza viruses, all of which have resulted in the emergence of resistant virus strains. The most recent example is baloxavir marboxil, where a single mutation in the active site of the target endonuclease domain of the RNA-dependent-RNA polymerase renders the recent FDA approved compound ∼1000-fold less effective. Raltegravir is a first-in-class HIV inhibitor that shows modest activity to the endonuclease. Here, we have used structure-guided approaches to create rationally designed derivative molecules that efficiently engage the endonuclease active site. The design strategy was driven by our previously published structures of endonuclease-substrate complexes, which allowed us to target functionally conserved residues and reduce the likelihood of resistance mutations. We succeeded in developing low nanomolar equipotent inhibitors of both wild-type and baloxavir-resistant endonuclease. We also developed macrocyclic versions of these inhibitors that engage the active site in the same manner as their 'open' counterparts but with reduced affinity. Structural analyses provide clear avenues for how to increase the affinity of these cyclic compounds.


Assuntos
Dibenzotiepinas , Inibidores de Integrase de HIV , Influenza Humana , Orthomyxoviridae , Humanos , RNA Polimerase Dependente de RNA , Piridonas/farmacologia , Piridonas/uso terapêutico , Influenza Humana/tratamento farmacológico , Dibenzotiepinas/farmacologia , Dibenzotiepinas/uso terapêutico , Endonucleases , Triazinas/farmacologia , Antivirais/farmacologia
11.
BMC Pediatr ; 23(1): 35, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681802

RESUMO

BACKGROUND: Anti-influenza treatment is important for children and is recommended in many countries. This study assessed safety, clinical, and virologic outcomes of baloxavir marboxil (baloxavir) treatment in children based on age and influenza virus type/subtype. METHODS: This was a post hoc pooled analysis of two open-label non-controlled studies of a single weight-based oral dose of baloxavir (day 1) in influenza virus-infected Japanese patients aged < 6 years (n = 56) and ≥ 6 to < 12 years (n = 81). Safety, time to illness alleviation (TTIA), time to resolution of fever (TTRF), recurrence of influenza illness symptoms and fever (after day 4), virus titer, and outcomes by polymerase acidic protein variants at position I38 (PA/I38X) were evaluated. RESULTS: Adverse events were reported in 39.0 and 39.5% of patients < 6 years and ≥ 6 to < 12 years, respectively. Median (95% confidence interval) TTIA was 43.2 (36.3-68.4) and 45.4 (38.9-61.0) hours, and TTRF was 32.2 (26.8-37.8) and 20.7 (19.2-23.8) hours, for patients < 6 years and ≥ 6 to < 12 years, respectively. Symptom and fever recurrence was more common in patients < 6 years with influenza B (54.5 and 50.0%, respectively) compared with older patients (0 and 25.0%, respectively). Virus titers declined (day 2) for both age groups. Transient virus titer increase and PA/I38X-variants were more common for patients < 6 years. CONCLUSIONS: The safety and effectiveness of single-dose baloxavir were observed in children across all age groups and influenza virus types. Higher rates of fever recurrence and transient virus titer increase were observed in children < 6 years. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information JapicCTI-163,417 (registered 02 November 2016) and JapicCTI-173,811 (registered 15 December 2017).


Assuntos
Dibenzotiepinas , Influenza Humana , Orthomyxoviridae , Tiepinas , Criança , Humanos , Antivirais/efeitos adversos , Dibenzotiepinas/uso terapêutico , Febre/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Japão , Oxazinas/efeitos adversos , Piridinas/efeitos adversos , Piridonas , Tiepinas/uso terapêutico , Tiepinas/efeitos adversos , Triazinas/efeitos adversos
12.
ChemistryOpen ; 12(1): e202200203, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36599693

RESUMO

Heterocyclic systems are now considered to be an integral part of material chemistry. Thiophene, selenophene, furan, pyrrole, carbazole, triazine and others are some such examples worth mentioning. 2,4,6-Tri(thiophen-2-yl)-1,3,5-triazine is a C3h -symmetric system with thiophene as the donor unit and s-triazine as the acceptor unit. This review gives an insight into the advances made in the thienyl-triazine chemistry over the past two to three decades. The synthetic pathways for arriving at this system and all its important derivatives are provided. The major focus is on the materials synthesized using the thienyl-triazine system, including star molecules, linear and hyperbranched polymers, porous materials and their diverse applications. This review will play a catalytic role for new dimensions to be explored in thienyl-triazine chemistry.


Assuntos
Tiofenos , Triazinas , Tiofenos/química , Triazinas/química , Polímeros/química , Catálise , Porosidade
13.
J Enzyme Inhib Med Chem ; 38(1): 398-404, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36476046

RESUMO

The non-receptor protein tyrosine phosphatase (PTP) SHP2 encoded by the PTPN11 gene is a critical regulator in a number of cellular signalling processes and pathways, including the MAPK and the immune-inhibitory programmed cell death PD-L1/PD-1 pathway. Hyperactivation and inactivation of SHP2 is of great therapeutic interest for its association with multiple developmental disorders and cancer-related diseases. In this work, we characterised a potent SHP2 allosteric inhibitor 2-((3 R,4R)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-5-(2,3-dichlorophenyl)-3-methylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (PB17-026-01) by using structure-based design. To study the structure-activity relationship, we compared co-crystal structures of SHP2 bound with PB17-026-01 and its analogue compound PB17-036-01, which is ∼20-fold less active than PB17-026-01, revealing that both of the compounds are bound to SHP2 in the allosteric binding pocket and PB17-026-01 forms more polar contacts with its terminal group. Overall, our results provide new insights into the modes of action of allosteric SHP2 inhibitor and a guide for the design of SHP2 allosteric inhibitor.


Assuntos
Triazinas , Triazinas/farmacologia , Cristalografia por Raios X , Proteína Tirosina Fosfatase não Receptora Tipo 11
14.
Acta Trop ; 238: 106797, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36528088

RESUMO

The phylum Apicomplexa contains some of the most serious human and veterinary parasites, including Eimeria magna, Toxoplasma gondii, and many others. Toltrazuril (TOL) has activity against multiple stages of Apicomplexan parasites, but its clinical use is limited by low bioavailability. In present study, we prepared one new formulation named the microenvironment pH modified solid dispersion (pHM-SD), which was composed of three components including Ca(OH)2, TOL, and PVPk30 with the weight ratio of 1:8:8. In vivo evaluation for bioavailability and efficacy of the pHM-SD was conducted following oral administration and hypodermic injection. The performance of the pHM-SD was also contrast to corresponding results of raw material drug and commercial Baycox® to evaluate the advantages for clinical application. The results showed that the bioavailability of prototype TOL and its active metabolites toltrazuril sulfoxide (TOLSO), toltrazuril sulfone (TOLSO2) in rabbits were improved remarkably after oral administration of the pHM-SD. The safety of the pHM-SD via oral administration was adequately verified via the histopathological examination. We subsequently evaluated effects of the pHM-SD on Eimeria magna oocysts and Toxoplasma gondii tachyzoites. In vivo anti-coccidia efficacy further confirmed that the pHM-SD could be used as a strategy to minimize the oocyst exposure. In vitro cytotoxicity and anti-Toxoplasma tests showed that the pHM-SD had little damage to host cells within the concentration of 100 µg/ mL, and the anti-Toxoplasma efficacy was significantly improved compared with TOL. Combined with the above-mentioned experimental results, we conclude that the pHM-SD maybe a promising candidate for providing better clinical outcomes.


Assuntos
Coccidiose , Eimeria , Toxoplasma , Animais , Humanos , Coelhos , Triazinas/uso terapêutico , Triazinas/farmacologia , Concentração de Íons de Hidrogênio , Coccidiose/veterinária
15.
Mar Pollut Bull ; 186: 114460, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521363

RESUMO

This study investigated the distribution of triazine herbicides in the Laizhou Bay, China and found that the total concentrations of triazine herbicides in the seawater and sediments were 111.15-234.85 ng/L and 0.902-4.661 µg/kg, respectively. Triazine herbicides especially ametryn, atrazine, and simazine were negatively correlated with prokaryote diversity in the seawater. While ametryn, desethylatrazine and desisopropylatrazine had positively significant effects on eukaryotes Dinophyceae, Bacillariophyta, and Cercozoa in the sediments. Moreover, the degree of fragmentation of eukaryotic networks increased dramatically with the increasing numbers of removed nodes, but prokaryotic networks did not change with the decrease of nodes. In addition, the stability analysis and neutral community models revealed that eukaryotes were more sensitive to triazine herbicides than prokaryotes. These results suggest that triazine herbicides might affect the structure and interactions of microbial communities. Therefore, more attentions should be paid to the ecological risk of triazine herbicides in marine ecosystems.


Assuntos
Atrazina , Herbicidas , Microbiota , Baías , Herbicidas/análise , Triazinas/análise , Atrazina/análise
16.
Sci Total Environ ; 807(Pt 1): 150609, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34619212

RESUMO

Triazine herbicides are widely used in agricultural production, and large amounts of herbicide residue enter the ocean through surface runoff. In this study, the toxicities of the triazine herbicides atrazine, prometryn and terbutryn (separately and mixed) to Phaeodactylum tricornutum were investigated. The EC50 values of atrazine, prometryn and terbutryn were 28.38 µg L-1, 8.86 µg L-1, and 1.38 µg L-1, respectively. The EC50 of an equitoxic mixture of the three herbicides was 0.78 TU, indicating that they had synergistic effects. The equitoxic mixture accumulated in P. tricornutum, which damaged chloroplast and mitochondria structures and significantly decrease the biomass, levels of key cellular components (such as chlorophyll a (chl a), carbon (C) and nitrogen (N) content, fatty acid content) and the effective photochemical quantum yield of photosystem II (PSII, ∆Fv/Fm). The mixture also downregulated key genes in the light response (PsbD, PetF), dark response (PGK, PRK), tricarboxylic acid (TCA) cycle (CS, ID, OGD, and MS) and fatty acid synthesis (FABB, SCD, and PTD9). P. tricornutum partially alleviates the effects of the mixture on photosynthesis and fatty acid synthesis by upregulating PetD, PsaB, RbcL and FabI expression. The triazine herbicide mixture reduced the biomass and nutritional value of marine phytoplankton by inhibiting photosynthesis and energy metabolism.


Assuntos
Atrazina , Herbicidas , Atrazina/toxicidade , Clorofila A , Herbicidas/toxicidade , Valor Nutritivo , Fotossíntese , Prometrina , Triazinas/toxicidade
17.
Eur Rev Med Pharmacol Sci ; 26(22): 8567-8575, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36459037

RESUMO

OBJECTIVE: Proteostasis is an important process occurring in all living cells and is highly indispensable for cell survival. The HslVU protease/chaperone complex's critical role in regulating proteostasis to maintain a healthy cellular proteome and its presence in pathogenic microbes made it an important drug target. This study aimed to identify small molecular inhibitors of the HslV protease. MATERIALS AND METHODS: Herein, a library of small molecules belonging to the triazine and chromone families has been evaluated for their inhibitory potential against the E. coli HslV protease using both in silico and in vitro techniques. RESULTS: Four compounds, i.e., SHS-II-123a, SHS-II-147a, US-IV-89, and US-IV-92, were identified as potential inhibitors of the HslV protease having IC50 values in the range of 0.1 to 0.32 µM. Additionally, these compounds' drug-likeness and ADMET profiles indicated their compatibility to be considered safer drug candidates. CONCLUSIONS: To the best of our knowledge, this is the first report on small molecules having inhibitory effects on the HslVU complex. These identified compounds can be efficiently subjected to further investigations to develop novel and safer antimicrobial agents.


Assuntos
Cromonas , Peptídeo Hidrolases , Humanos , Cromonas/farmacologia , Triazinas/farmacologia , Tiazóis , Escherichia coli , Endopeptidases , Chaperonas Moleculares
18.
Pestic Biochem Physiol ; 188: 105263, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464368

RESUMO

The leafminer Liriomyza trifolii is an important insect pest of ornamental and vegetable crops worldwide. Cyromazine is an effective, commonly-used insecticide that functions as a growth regulator, but its effect on L. trifolii has not been previously reported. In this study, transcriptome analysis was undertaken in L. trifolii exposed to cyromazine. Clusters of orthologous groups analysis indicated that a large number of differentially expressed genes responding to cyromazine were categorized as "lipid transport and metabolism", "post-translational modification, protein turnover, chaperones", and "cell wall/membrane/envelope biogenesis". Gene ontology analysis indicated that pathways associated with insect hormones, growth and development, and cuticle synthesis were significantly enriched. In general, the transcriptome results showed that the genes related to insect hormones were significantly expressed after treatment with cyromazine. Furthermore, the combined exposure of L. trifolii to cyromazine and the hormone analogues 20-hydroxyecdysone (20E) or juvenile hormone (JH) indicated that hormone analogues can change the expression pattern of hormone-related genes (20EP and JHEH) and pupal length. The combined application of cyromazine with 20E improved the survival rate of L. trifolii, whereas the combination of JH and cyromazine reduced survival. The results of this study help elucidate the mechanistic basis for cyromazine toxicity and provide a foundation for understanding cyromazine resistance.


Assuntos
Dípteros , Hormônios de Inseto , Inseticidas , Animais , Dípteros/genética , Inseticidas/toxicidade , Triazinas/toxicidade , Hormônios Juvenis/farmacologia
19.
Pestic Biochem Physiol ; 188: 105271, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464376

RESUMO

The acute toxicity of chlorpyrifos and chlorpyrifos-oxon (organophosphorothioate insecticides) was examined alone and in combination with atrazine (triazine herbicide) and alachlor (chloroacetanilide herbicide) to honey bees (Apis mellifera). Atrazine and alachlor were observed to not be acutely toxic to bees at doses up to 10 and 4 µg per bee, respectively. However, atrazine significantly increased chlorpyrifos toxicity by 3-fold while reducing chlorpyrifos-oxon toxicity by 1.8-fold. These changes in toxicity are correlated with significant 1.3- and 1.2-fold inhibition of acetylcholinesterase (AChE) activity in bees exposed to chlorpyrifos and chlorpyrifos-oxon, respectively. Atrazine significantly increased cytochrome P450, general esterase, and glutathione S-transferase (GST) activities by 1.5-, 1.2-, and 1.2- fold respectively, in bees compared to untreated individuals. Alachlor increased chlorpyrifos toxicity by 2.5-fold but did not affect the toxicity of chlorpyrifos-oxon. Exposure to alachlor and chlorpyrifos did not affect AChE compared to chlorpyrifos alone. However, exposure to chlorpyrifos-oxon and alachlor significantly increased acetylcholinesterase (AChE) activity by 1.4-fold. GST activity, but not P450 or general esterases, was significantly increased in bees exposed to alachlor. These data provide evidence that triazine and chloroacetanilide herbicide exposure alters detoxification enzyme activity and, in turn, alters the sensitivity of bees to organophosphorothioate insecticides. Importantly, these data can be used to guide future studies aiming to test safety profiles for pollinators and expand regulatory framework required for pesticide registration.


Assuntos
Atrazina , Clorpirifos , Inseticidas , Abelhas , Animais , Atrazina/toxicidade , Clorpirifos/toxicidade , Acetilcolinesterase , Inseticidas/toxicidade , Triazinas , Esterases
20.
J Phys Chem B ; 126(50): 10758-10767, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36502412

RESUMO

Understanding the interactions and thermodynamic parameters that govern the structure and stability of supramolecular polymers is challenging because of their flexible nature and high sensitivity to weak intermolecular interactions. The application of both experimental and computational analyses reveals the role that substituents on cyanuric acid (Cy), and other nitrogen-containing heterocycles, play in the formation of novel helical supramolecular structures. In this report, we focus on how noncovalent interactions, including steric and stacking interactions, modulate the structural and physical properties of these assemblies. In-depth analyses and several examples of critical steric and electrostatic effects provide insight into the relationship between intermolecular interactions of Cy with nucleic acids and the structure and thermodynamic stability of the supramolecular polymers they form.


Assuntos
DNA , Polímeros , Polímeros/química , Triazinas/química , Termodinâmica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...