Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.048
Filtrar
Mais filtros










Filtros aplicados

Base de dados
Intervalo de ano de publicação
1.
Ecotoxicology ; 29(5): 607-612, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32291615

RESUMO

The effect of temperature on the toxicities of four diamide insecticides (chlorantraniliprole, cyantraniliprole, flubendiamide, tetraniliprole) against three lepidopteran insects (Helicoverpa armigera, Plutella xylostella, Athetis lepigone) were determined from 15 to 35 °C by exposing third-instar larvae to dip-treated cabbage leaf. The results indicated that increase in temperature led to an increase significantly and regularly in the toxicities of the four diamide insecticides against P. xylostella and H. armigera, but not for A. lepigone. The temperature coefficients (TCs) of the four diamide insecticides increased from 15 to 35 °C. Tetraniliprole for H. armigera (+825.83), chlorantraniliprole for P. xylostella (+315.65) and cyantraniliprole for H. armigera (+225.77) exhibited high positive TCs. For A. lepigone, temperature had a positively weak or no effect on the toxicities of most of the diamide insecticides from 20 to 30 °C, but a higher effect from 30 to 35 °C. In addition, the toxicities of chlorantraniliprole, cyantraniliprole and tetraniliprole all decreased from 15 to 20 °C. This study can guide pest managers in choosing suitable ambient field temperature when spraying diamide insecticides against lepidopteran insects.


Assuntos
Diamida/toxicidade , Insetos , Inseticidas/toxicidade , Animais , Benzamidas , Larva , Mariposas , Pirazóis , Sulfonas , Temperatura , Testes de Toxicidade , ortoaminobenzoatos
2.
Chemosphere ; 249: 126479, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32208218

RESUMO

As part of a new generation of diamide insecticides, cyantraniliprole has broad application prospects. In the present study, a QuEChERS-UPLC-MS/MS method was established to determine the residues of cyantraniliprole and its main metabolite J9Z38 in soil and earthworms. Moreover, the accumulation and toxicity of cyantraniliprole and J9Z38 in earthworms were evaluated. The present results show that the detection method of cyantraniliprole and J9Z38 has high sensitivity and accuracy, which could be used for the accurate quantification of cyantraniliprole and J9Z38 residues in soil and earthworms. Additionally, cyantraniliprole degraded faster than its main metabolite J9Z38 in the artificial soil. Moreover, the bioenrichment efficiency of cyantraniliprole was higher than J9Z38. The toxicity test result showed that cyantraniliprole and J9Z38 could induce oxidative stress effect in earthworms from 5.0 mg/kg, finally resulting in cellular damage. Moreover, the oxidative damage degree induced by cyantraniliprole was higher than J9Z38. Combining the results of residue test and toxicity test, although cyantraniliprole degraded faster than its main metabolite J9Z38 in the artificial soil, its risk to earthworms was higher than J9Z38.


Assuntos
Inseticidas/toxicidade , Resíduos de Praguicidas/toxicidade , Pirazóis/toxicidade , ortoaminobenzoatos/toxicidade , Animais , Cromatografia Líquida , Diamida , Inseticidas/análise , Oligoquetos/efeitos dos fármacos , Resíduos de Praguicidas/análise , Pirazóis/análise , Solo/química , Poluentes do Solo/análise , Espectrometria de Massas em Tandem/métodos , Testes de Toxicidade , ortoaminobenzoatos/análise
3.
J Agric Food Chem ; 68(6): 1731-1740, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31951399

RESUMO

Diamide insecticides targeting ryanodine receptors (RyRs) are a major class of pesticides used to control a wide range of agricultural pests, but their efficacies have been reduced dramatically by the recent emergence of resistance mutations. There is a pressing need to develop novel insecticides, targeting distinct and novel binding sites within insect RyRs to overcome the resistance crisis; however, the limited structural information on insect RyRs is a major roadblock to our understanding of their molecular mechanisms. Here, we report the crystal structure of the RyR SPRY2 domain from the diamondback moth (DBM), Plutella xylostella, a destructive agricultural pest worldwide that has developed resistance to all classes of insecticide at 2.06 Å resolution. The overall fold of DBM SPRY2 is similar to its mammalian homolog, but it shows distinct conformations in several loops. Docking it into the recently published cryo-electron microscope structure of the full-length RyR reveals that two insect-specific loops interact with the BSol domain from the neighboring subunit. The SPRY2-BSol interface will change the conformation upon channel gating, indicating that it might be a potential targeting site for insect-specific insecticides. Interestingly, several previously identified disease-causing mutations also lie in the same interface, implying that this interface is important for channel gating. Another insect-specific loop located in the SPRY2-SPRY3 interface might indirectly affect another gating interface between SPRY3 and Repeat34.


Assuntos
Diamida/química , Proteínas de Insetos/química , Inseticidas/química , Mariposas/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Animais , Diamida/farmacologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inseticidas/farmacologia , Simulação de Acoplamento Molecular , Mariposas/química , Mariposas/efeitos dos fármacos , Mariposas/genética , Domínios Proteicos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
4.
Pest Manag Sci ; 76(1): 47-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31157506

RESUMO

BACKGROUND: Fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), a major lepidopteran pest in Latin and North America, has very recently invaded the continents of Africa and Asia. FAW has evolved resistance to different insecticides and transgenic corn expressing Bacillus thuringiensis (Bt) toxins. Here, we investigated the extent and mechanisms of resistance to diamide insecticides in a Brazilian field-collected FAW strain selected using chlorantraniliprole. RESULTS: Continuous laboratory selection of a field-collected FAW strain with chlorantraniliprole resulted in resistance ratios of 225-fold and > 5400-fold against chlorantraniliprole and flubendiamide, respectively, when compared with a susceptible strain. Pre-exposure to different synergists known to inhibit detoxification enzymes did not result in significantly increased larval toxicity, suggesting a minor role for metabolic resistance. Sequencing of the FAW ryanodine receptor (RyR) C-terminal domains II to VI revealed a single nucleotide polymorphism, resulting in a I4734M mutation recently said to confer target-site resistance to diamides in lepidopteran pests. Genotyping by pyrosequencing of field-collected FAW larvae sampled in the 2018 crop season suggests a low resistance allele frequency. Furthermore, we developed a fluorescent polymerase chain reaction (PCR)-based allelic discrimination assay for rapid genotyping of field-collected FAW samples, because diamides are increasingly used in Bt-/non-Bt corn. CONCLUSIONS: Recently, the identified RyR mutation has been shown to confer field resistance in other lepidopteran pests such as diamondback moth, tomato leafminer and striped rice stem borer. The developed PCR-based allelic discrimination assay will help to monitor the frequency and future spread of diamide resistance allele in FAW field populations and help to implement appropriate resistance management measures. © 2019 Society of Chemical Industry.


Assuntos
Spodoptera , Animais , Diamida , Resistência a Inseticidas , Inseticidas , Larva , Mutação , Canal de Liberação de Cálcio do Receptor de Rianodina
5.
J Agric Food Chem ; 67(48): 13344-13352, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31721573

RESUMO

A series of novel anthranilic diamide derivatives (5a-5ab) containing moieties of trifluoromethylpyridine and hydrazone was designed and synthesized. The synthesized compounds were evaluated in vivo for their activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Most of the synthesized compounds displayed good to excellent antiviral activities. The compounds 5i, 5k, 5s, 5w, 5x, and 5z had the curative activity over 65% against TMV at the concentration of 500 µg/mL, which were significantly higher than those of ningnanmycin (55.0%) and ribavirin (37.9%). Notably, the curative activity of compound 5i was up to 79.5%, with the EC50 value of 75.9 µg/mL, whereas the EC50 value of ningnanmycin was 362.4 µg/mL. The pot experiments also further demonstrated the significantly curative effect of 5i. Meanwhile, compounds 5h, 5p and 5x displayed more protective activities on TMV than that of ningnanmycin. Moreover, compounds 5a, 5e, 5f, and 5i showed inactivation activity similar to ningnanmycin at 500 µg/mL, and the EC50 value of 5e (41.5 µg/mL) was lower than ningnanmycin (50.0 µg/mL). The findings of transmission electron microscopic (TEM) indicated that the synthesized compounds exhibited strong and significant binding affinity to TMV coat protein (CP) and could obstruct the self-assembly and increment of TMV particles. Microscale thermophoresis (MST) studies on TMV-CP and CMV CP revealed that some of the active compounds, particularly 5i, exhibited a strong binding capability to TMV-CP or CMV-CP. This study revealed that anthranilic diamide derivatives containing moieties of trifluoromethylpyridine and hydrazone could be used as novel antiviral agents for controlling the plant viruses.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Diamida/química , Hidrazonas/química , Vírus de Plantas/efeitos dos fármacos , Piridinas/química , Antivirais/química , Cucumovirus/efeitos dos fármacos , Cucumovirus/crescimento & desenvolvimento , Diamida/farmacologia , Desenho de Fármacos , Hidrazonas/farmacologia , Testes de Sensibilidade Microbiana , Vírus de Plantas/crescimento & desenvolvimento , Piridinas/síntese química , Piridinas/farmacologia , Relação Estrutura-Atividade , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/crescimento & desenvolvimento
6.
Molecules ; 24(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547559

RESUMO

Novel anthranilic diamides with sulfilimidoyl and sulfoximidoyl functionalities were successfully prepared. Among newly-prepared organosulfur compounds, 3-bromo-1-(3-chloropyridin-2-yl)-N-(2-methyl-6-(methylcarbamoyl)-4-(methylthio)phenyl)-1H-pyrazole-5-carboxamide and (S,E)-3-bromo-1-(3-chloropyridin-2-yl)-N-(2-methyl-4-(S-methyl-N-(2,2,2-trifluoroacetyl)sulfinimidoyl)-6-(methylcarbamoyl)phenyl)-1H-pyrazole-5-carboxamide showed good levels of efficacy and a strong correlation between insecticidal activities and physical properties, respectively. In particular, available data indicated that the N-trifluoroacetyl sulfilimine moiety could be an appealing structural scaffold for the discovery of a new crop-protecting agent.


Assuntos
Antivirais/síntese química , Diamida/química , Isoxazóis/química , Animais , Antivirais/farmacologia , Cromatografia em Camada Delgada , Inseticidas/síntese química , Inseticidas/farmacologia , Spodoptera/efeitos dos fármacos , Relação Estrutura-Atividade
7.
J Agric Food Chem ; 67(39): 10977-10983, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490679

RESUMO

In this study, an analytical method was developed and validated for simultaneous determination of five diamide insecticides (chlorantraniliprole, cyantraniliprole, flubendiamide, cyclaniliprole, and tetrachlorantraniliprole) in food matrices. Determination of the latter two diamide compounds is first reported. Samples were cleaned up by multiplug filters containing carbon nanotubes (CNT) or hydrophilic-lipophilic balanced copolymers (HLB) and classic dispersive solid phase extraction (d-SPE) procedures, respectively. The CNT multiplug filter performed the best in terms of process rapidity and cleanup efficiency; thus, it was finally chosen for sample cleanup. Instrumental analysis was completed in 5 min using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Mean recoveries of the five diamides ranged from 84.3 to 110.0%, with intraday and interday relative standard deviations (RSD) of less than 13.5%. Limits of quantitation (LOQ) of all analytes ranged from 0.005 to 0.01 mg kg-1 in different matrices. The results indicate this method is reliable for monitoring the five diamide insecticides in various foods.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Diamida/química , Filtração/métodos , Contaminação de Alimentos/análise , Inseticidas/química , Resíduos de Praguicidas/química , Espectrometria de Massas em Tandem/métodos , Diamida/isolamento & purificação , Filtração/instrumentação , Inseticidas/isolamento & purificação , Nanotubos de Carbono/química , Resíduos de Praguicidas/isolamento & purificação
8.
J Pharmacol Sci ; 140(1): 43-47, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31036520

RESUMO

This study investigated the effects of thiol and heme oxidants on responsiveness to cGMP generators in isolated rat aorta and pulmonary artery using an organ chamber. The nitric oxide (NO) donor sodium nitroprusside (SNP)-induced relaxation was impaired by exposure to the thiol oxidant diamide in both the aorta and the pulmonary artery, whereas the soluble guanylate cyclase (sGC) stimulator BAY 41-2272- or the sGC activator BAY 60-2770-induced relaxation was not affected. The impairment by diamide of SNP-induced aortic and pulmonary arterial relaxation was completely restored by post-treatment with the thiol reductant dithiothreitol. However, regardless of the vessel type, the relaxant response to SNP or BAY 41-2272 was impaired by exposure to the heme oxidant ODQ, whereas the response to BAY 60-2770 was enhanced. The ODQ-induced effects were reversed partially by post-treatment with the heme reductant dithionite. These findings indicate that thiol oxidation attenuates only the vascular responsiveness to NO donors and that heme oxidation attenuates the responsiveness to NO donors and sGC stimulators but augments that to sGC activators. Therefore, under oxidative stress, the order of usability of the vasodilators is suggested to be: NO donors < sGC stimulators < sGC activators.


Assuntos
Aorta/efeitos dos fármacos , Benzoatos/farmacologia , Compostos de Bifenilo/farmacologia , GMP Cíclico/metabolismo , Diamida/farmacologia , Hidrocarbonetos Fluorados/farmacologia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Oxidantes/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Pirazóis/farmacologia , Piridinas/farmacologia , Compostos de Sulfidrila/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Ditiotreitol/farmacologia , Técnicas In Vitro , Masculino , Estresse Oxidativo , Ratos Wistar , Guanilil Ciclase Solúvel/metabolismo
9.
Gen Physiol Biophys ; 38(2): 183-186, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30821253

RESUMO

Very recently, the diamide insecticide chlorantraniliprole was shown to induce Ca2+-release from sarcoplasmic reticulum (SR) vesicles isolated from mammalian skeletal muscle through the activation of the SR Ca2+ channel ryanodine receptor. As this result raises severe concerns about the safety of this chemical, we aimed to learn more about its action. To this end, single-channel analysis was performed, which showed that chlorantraniliprole induced high-activity bursts of channel opening that accounts for the Ca2+-releasing action described before.


Assuntos
Inseticidas , Canal de Liberação de Cálcio do Receptor de Rianodina , ortoaminobenzoatos , Animais , Cálcio , Diamida , Inseticidas/farmacologia , Músculo Esquelético , Rianodina , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos , Retículo Sarcoplasmático , ortoaminobenzoatos/farmacologia
10.
Chemistry ; 25(28): 6928-6940, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-30807667

RESUMO

Two novel solid reagents-1-sulfonimidoyl- and 1-sulfamimidoyl-3-methylimidazolium derivatives-for the synthesis of sulfonimidamides and imidosulfuric diamides, respectively, were developed. It is shown that these reagents are very effective in substitution reactions with various N- and O-nucleophiles; therefore, they significantly extend the accessibility to the chemical space covered by organosulfur(VI) compounds with S=N bonds. In addition, previously unknown imidosulfuric diamides with free imino nitrogen groups were prepared, and their physical and chemical properties were characterized (including molecular geometry, pKa , Log P, microsomal stability, and reactivity towards typical electrophiles). Similar to other organosulfur(VI) derivatives with S=N bonds, these compounds can be considered as promising bioisosteres of amides, ureas, or sulfonamides.


Assuntos
Diamida/síntese química , Imidas/síntese química , Sulfonamidas/síntese química , Compostos de Enxofre/síntese química , Animais , Técnicas de Química Sintética/métodos , Diamida/química , Diamida/metabolismo , Imidas/química , Imidas/metabolismo , Indicadores e Reagentes , Camundongos , Microssomos/metabolismo , Modelos Moleculares , Sulfonamidas/química , Sulfonamidas/metabolismo , Compostos de Enxofre/química , Compostos de Enxofre/metabolismo , Difração de Raios X
11.
Pest Manag Sci ; 75(10): 2682-2689, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30761724

RESUMO

BACKGROUND: Understanding the genetic basis of insect resistance to insecticides can help to implement insecticide resistance management (IRM) strategies. In this study, we selected a strain of Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) resistant to chlorantraniliprole using the F2 screen method, characterized the inheritance of resistance and evaluated patterns of cross-resistance to other diamide insecticides. RESULTS: The chlorantraniliprole-resistant strain (Chlorant-R) was selected from a field-collected population with an estimated allele frequency of 0.1316. The estimated median lethal concentration (LC50 ) values were 0.011 and 2.610 µg a.i. cm-2 for the susceptible (Sus) and Chlorant-R strains, respectively, resulting in a resistance ratio (RR) of 237-fold. The LC50 values of the reciprocal crosses were 0.155 and 0.164 µg a.i. cm-2 , indicating that resistance is autosomally inherited. Resistance was characterized as incompletely recessive and monogenic at concentrations close to the recommended field rates of chlorantraniliprole. Survival of the resistant strain and heterozygous larvae in maize plants treated at the field rate was ∼ 60 (similar to the susceptible strain on untreated maize) and 15%, respectively. The Chlorant-R strain showed low cross-resistance to cyantraniliprole (RR ∼ 27-fold) and very high cross-resistance to flubendiamide (RR > 42 000-fold). CONCLUSIONS: The frequency of chlorantraniliprole resistance allele was moderately high in a field-collected population of S. frugiperda. The inheritance of chlorantraniliprole resistance was characterized as autosomal, incompletely recessive and monogenic. S. frugiperda showed cross-resistance to other diamide insecticides. These results provide essential information for the implementation of IRM programs to preserve the useful life of diamide insecticides for controlling S. frugiperda in Brazil. © 2019 Society of Chemical Industry.


Assuntos
Hereditariedade/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Larva/genética , Spodoptera/genética , ortoaminobenzoatos/farmacologia , Animais , Diamida/farmacologia , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Spodoptera/efeitos dos fármacos , Spodoptera/crescimento & desenvolvimento
12.
BMC Microbiol ; 19(1): 26, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30691388

RESUMO

BACKGROUND: Previous reports showed that mutagenesis in nutrient-limiting conditions is dependent on Mfd in Bacillus subtilis. Mfd initiates one type of transcription-coupled repair (TCR); this type of repair is known to target bulky lesions, like those associated with UV exposure. Interestingly, the roles of Mfd in repair of oxidative-promoted DNA damage and regulation of transcription differ. Here, we used a genetic approach to test whether Mfd protected B. subtilis from exposure to two different oxidants. RESULTS: Wild-type cells survived tert-butyl hydroperoxide (t-BHP) exposure significantly better than Mfd-deficient cells. This protective effect was independent of UvrA, a component of the canonical TCR/nucleotide excision repair (NER) pathway. Further, our results suggest that Mfd and MutY, a DNA glycosylase that processes 8-oxoG DNA mismatches, work together to protect cells from lesions generated by oxidative damage. We also tested the role of Mfd in mutagenesis in starved cells exposed to t-BHP. In conditions of oxidative stress, Mfd and MutY may work together in the formation of mutations. Unexpectedly, Mfd increased survival when cells were exposed to the protein oxidant diamide. Under this type of oxidative stress, cells survival was not affected by MutY or UvrA. CONCLUSIONS: These results are significant because they show that Mfd mediates error-prone repair of DNA and protects cells against oxidation of proteins by affecting gene expression; Mfd deficiency resulted in increased gene expression of the OhrR repressor which controls the cellular response to organic peroxide exposure. These observations point to Mfd functioning beyond a DNA repair factor in cells experiencing oxidative stress.


Assuntos
Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/genética , Proteínas de Bactérias/genética , Reparo do DNA , Oxidantes/farmacologia , Estresse Oxidativo , Fatores de Transcrição/genética , DNA Glicosilases/genética , Diamida/farmacologia , Mutação , Transcrição Genética , terc-Butil Hidroperóxido/farmacologia
13.
Pest Manag Sci ; 75(4): 1034-1044, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30230239

RESUMO

BACKGROUND: Anthranilic diamide insecticides control lepidopteran pests through selectively binding and activating insect ryanodine receptors. In order to search for potential insecticides targeting the ryanodine receptors, a series of anthranilic diamide analogs including trifluoromethyl, nitro, or chloro groups were designed and synthesized by the principle of bioisosterism and structural optimization. RESULTS: Insecticidal data indicated that some compounds displayed good activity against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). In particular, the larvicidal activity of 6p against P. xylostella was 95% at 0.01 mg L-1 , equivalent to chlorantraniliprole (85%, 0.01 mg L-1 ). The comparative molecular similarity index analysis model obtained indicated that hydrogen bond acceptor and electron-withdrawing groups in the R'3 group are favourable for insecticidal activity against M. separata, which is consistent with the structure-activity relationships. Moreover, the calcium imaging experiment indicated, like chlorantraniliprole, that 6h and 6p are interacting with the ryanodine receptor. CONCLUSION: Introducing trifluoromethyl, nitro, or chloro groups to a specific position in the N-phenylpyrazole could improve or maintain the activity against M. separata and P. xylostella. 6h and 6p could be used as potential lead compounds for ryanodine receptor modulators. © 2018 Society of Chemical Industry.


Assuntos
Diamida/análogos & derivados , Inseticidas/química , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Animais , Diamida/química , Diamida/farmacologia , Desenho de Fármacos , Isoxazóis/química , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Modelos Químicos , Mariposas/crescimento & desenvolvimento , Relação Quantitativa Estrutura-Atividade , Canal de Liberação de Cálcio do Receptor de Rianodina
14.
Mini Rev Med Chem ; 19(1): 22-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29600763

RESUMO

Ryanodine receptors (RyRs) are calcium channels located on the endo(sarco)plasmic reticulum of muscle cells and neurons. They regulate the release of stored intracellular calcium and play a critical role in muscle contraction. The N-terminal part of these receptors accounts for roughly 80% and contains the binding sites for diverse RyRs modulators. The C-terminal domain contains the transmembrane region. This review summarizes the current knowledge about the molecular biology of insect RyRs, chemicals targeting mammal or insect RyRs, and the reasons for mammal RyR-related diseases and diamides resistances. It may lay the foundation for effective management of mammal RyR-related diseases and diamides resistances.


Assuntos
Descoberta de Drogas , Controle de Insetos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Rianodina/análogos & derivados , Rianodina/farmacologia , Animais , Diamida/análogos & derivados , Diamida/farmacologia , Diamida/toxicidade , Descoberta de Drogas/métodos , Humanos , Controle de Insetos/métodos , Insetos/efeitos dos fármacos , Insetos/metabolismo , Resistência a Inseticidas , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/toxicidade , Rianodina/toxicidade , Canal de Liberação de Cálcio do Receptor de Rianodina/química
15.
Nat Prod Res ; 33(17): 2453-2460, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29569471

RESUMO

Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC50 value of 0.158 mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC50 values of 0.067, 0.048 and 0.059 mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.


Assuntos
Diamida/química , Fungicidas Industriais/farmacologia , Herbicidas/síntese química , Herbicidas/farmacologia , Fenazinas/química , Echinochloa/efeitos dos fármacos , Fungicidas Industriais/síntese química , Herbicidas/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Relação Estrutura-Atividade
16.
Bioorg Chem ; 84: 399-409, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30551066

RESUMO

A new series of diamide functional compounds has been designed, synthesized and confirmed by spectroscopic methods and elemental analyses. All the synthesized compounds were evaluated for their antiproliferative activity on HepG2 cell line. Compounds 3k and 3l were proved to have potent anticancer activity equipotent or more potent than reference compound Combretastatin A-4. The results of DNA flow cytometry analysis demonstrated cell cycle arrest at G2/M phase. The extent of apoptosis induced by 3k and 3l was also determined. Moreover, the compounds produced a significant reduction in cellular microtubules for microtubule loss and potently inhibited the binding of [3H]colchicine to tubulin. Compounds 3k and 3l were proved to upregulate expression of proteins triggering apoptosis, such as p53, Bax, and decreased Bcl-2 overexpression as well as increased the expression of effector caspase- 3/7.


Assuntos
Antimitóticos/síntese química , Apoptose , Diamida/química , Desenho de Fármacos , Moduladores de Tubulina/síntese química , Antimitóticos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Diamida/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Relação Estrutura-Atividade , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-30524970

RESUMO

Dozens of Gram negative pathogens use one or more type III secretion systems (T3SS) to disarm host defenses or occupy a beneficial niche during infection of a host organism. While the T3SS represents an attractive drug target and dozens of compounds with T3SS inhibitory activity have been identified, few T3SS inhibitors have been validated and mode of action determined. One issue is the lack of standardized orthogonal assays following high throughput screening. Using a training set of commercially available compounds previously shown to possess T3SS inhibitory activity, we demonstrate the utility of an experiment pipeline comprised of six distinct assays to assess the stages of type III secretion impacted: T3SS gene copy number, T3SS gene expression, T3SS basal body and needle assembly, secretion of cargo through the T3SS, and translocation of T3SS effector proteins into host cells. We used enteropathogenic Yersinia as the workhorse T3SS-expressing model organisms for this experimental pipeline, as Yersinia is sensitive to all T3SS inhibitors we tested, including those active against other T3SS-expressing pathogens. We find that this experimental pipeline is capable of rapidly distinguishing between T3SS inhibitors that interrupt the process of type III secretion at different points in T3SS assembly and function. For example, our data suggests that Compound 3, a malic diamide, blocks either activity of the assembled T3SS or alters the structure of the T3SS in a way that blocks T3SS cargo secretion but not antibody recognition of the T3SS needle. In contrast, our data predicts that Compound 4, a haloid-containing sulfonamidobenzamide, disrupts T3SS needle subunit secretion or assembly. Furthermore, we suggest that misregulation of copy number control of the pYV virulence plasmid, which encodes the Yersinia T3SS, should be considered as a possible mode of action for compounds with T3SS inhibitory activity against Yersinia.


Assuntos
Sistemas de Secreção Tipo III/efeitos dos fármacos , Sistemas de Secreção Tipo III/metabolismo , Yersinia/efeitos dos fármacos , Yersinia/metabolismo , Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Sistemas de Secreção Bacterianos/efeitos dos fármacos , Sistemas de Secreção Bacterianos/genética , Sistemas de Secreção Bacterianos/metabolismo , Diamida/farmacologia , Dosagem de Genes , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Malatos/farmacologia , Plasmídeos/genética , Proteínas Tirosina Fosfatases/genética , Sistemas de Secreção Tipo III/genética , Virulência/genética , Yersinia/genética , Yersinia pseudotuberculosis/metabolismo
18.
Chem Biol Drug Des ; 92(5): 1914-1919, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29923690

RESUMO

Anthranilic diamides is a class of insecticides target at ryanodine receptors (RyRs). To discover potent insecticides targeting at RyRs, a series of novel anthranilic diamides with a diacylhydrazine bridge were designed and synthesized. Their insecticidal activities were evaluated and a preliminary structure-activity relationship (SAR) was summarized. In particular, compound 5g exhibited good lethality against oriental armyworm (Mythimna separata) at a concentration of 5 mg/L. The calcium imaging experimental results indicated that the compound 5g can serve as effective insect Ca2+ level modulators by disrupting the cellular calcium homeostasis in Mythimna separata (Walker) and Spodoptera exigua (Hübner), which probably activated the RyRs on the ER membrane.


Assuntos
Cálcio/metabolismo , Diamida/análogos & derivados , Hidrazinas/química , Inseticidas/síntese química , ortoaminobenzoatos/química , Animais , Diamida/síntese química , Diamida/farmacologia , Desenho de Fármacos , Inseticidas/química , Inseticidas/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Spodoptera/efeitos dos fármacos , Relação Estrutura-Atividade
19.
Bioorg Med Chem ; 26(12): 3541-3550, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-29866480

RESUMO

A series of novel anthranilic diamides derivatives (7a-s) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, 1H NMR, 13C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella). Above all, the larvicidal activity of 7o against oriental armyworm was 100% and 40% at 0.25 and 0.1 mg L-1, comparable to that of the standard chlorantraniliprole (100%, 0.25 mg L-1 and 20%, 0.1 mg L-1). What is more, 7o against diamondback moth displayed 90% insecticidal activity at 0.01 mg L-1, superior to chlorantraniliprole (45%, 0.01 mg L-1). The experiments 7o on the American cockroach (Periplaneta Americana) heart beating rates (Dorsal vessel) and contractile force were compared with chlorantraniliprole. In addition, 7o could affect the calcium homeostasis in the central neurons of the third larvae of oriental armyworm, which revealed that the ryanodine receptor is the potential target of 7o. The density functional theory (DFT) calculation results revealed the amide bridge, the benzene ring of anthraniloyl moiety and pyrazole ring might play an important role in the insecticidal activity through hydrophobic interactions and π-π conjugations.


Assuntos
Diamida/química , Inseticidas/síntese química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Animais , Baratas/efeitos dos fármacos , Baratas/fisiologia , Diamida/síntese química , Diamida/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Inseticidas/química , Inseticidas/toxicidade , Isoxazóis/química , Larva/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Mariposas/metabolismo , Teoria Quântica , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Relação Estrutura-Atividade
20.
Biochem J ; 475(11): 1909-1937, 2018 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-29626155

RESUMO

In all living organisms, coenzyme A (CoA) is an essential cofactor with a unique design allowing it to function as an acyl group carrier and a carbonyl-activating group in diverse biochemical reactions. It is synthesized in a highly conserved process in prokaryotes and eukaryotes that requires pantothenic acid (vitamin B5), cysteine and ATP. CoA and its thioester derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. A novel unconventional function of CoA in redox regulation has been recently discovered in mammalian cells and termed protein CoAlation. Here, we report for the first time that protein CoAlation occurs at a background level in exponentially growing bacteria and is strongly induced in response to oxidizing agents and metabolic stress. Over 12% of Staphylococcus aureus gene products were shown to be CoAlated in response to diamide-induced stress. In vitro CoAlation of S. aureus glyceraldehyde-3-phosphate dehydrogenase was found to inhibit its enzymatic activity and to protect the catalytic cysteine 151 from overoxidation by hydrogen peroxide. These findings suggest that in exponentially growing bacteria, CoA functions to generate metabolically active thioesters, while it also has the potential to act as a low-molecular-weight antioxidant in response to oxidative and metabolic stress.


Assuntos
Antioxidantes/metabolismo , Proteínas de Bactérias/metabolismo , Coenzima A/metabolismo , Staphylococcus aureus/metabolismo , Proteínas de Bactérias/genética , Coenzima A/genética , Diamida/farmacologia , Gliceraldeído-3-Fosfato Desidrogenases/genética , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Oxirredução , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA