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1.
J Agric Food Chem ; 67(38): 10782-10790, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31490683

RESUMO

Systematic investigation of cyproconazole, including absolute stereochemistry, fungicidal activity, quantification in two matrixes, and stereoselective degradation in cucumber, are conducted in this study. By virtue of vibrational circular dichroism (VCD) spectroscopy, absolute configurations of four stereoisomers were identified to be (2R,3R)-(+)-, (2R,3S)-(+)-, (2S,3S)-(-)-, and (2S,3R)-(-)-cyproconazoles. Then four stereoisomers exhibited stereoselective fungicidal activities against Fusarium graminearum Schw and Magnaporthe oryzae, and the order of fungicidal activity was (2S,3S)-(-)-stereoisomer > the stereoisomer mixture > (2S,3R)-(-)-stereoisomer > (2R,3R)-(+)-stereoisomer > (2R,3S)-(+)-stereoisomer. Moreover, chiral liquid chromatography-tandem mass spectrometry was used to identify and quantify cyproconazole stereoisomers in soil and cucumber matrixes. Good linearity (R2 ≥ 0.99) and recoveries (86.79-92.47%, RSD ≤ 3.94%) for them were achieved, individually. Furthermore, stereoselective degradation of four cyproconazole stereoisomers was observed in cucumber and the order of degradation rate was (2R,3R)-(+)-cyproconazole > (2S,3S)-(-)-cyproconazole > (2R,3S)-(+)-cyproconazole > (2S,3R)-(-)-cyproconazole. We envision that such systematic assessments of chiral fungicides at an enantiomeric level would provide valuable information in future studies involving enantioselective physiological, metabolic, and toxicological activities.


Assuntos
Fungicidas Industriais/química , Triazóis/química , Alternaria/efeitos dos fármacos , Alternaria/crescimento & desenvolvimento , Cromatografia Líquida de Alta Pressão , Cucumis sativus/química , Contaminação de Alimentos/análise , Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Rhizoctonia/efeitos dos fármacos , Rhizoctonia/crescimento & desenvolvimento , Poluentes do Solo/química , Poluentes do Solo/farmacologia , Estereoisomerismo , Espectrometria de Massas em Tandem , Triazóis/farmacologia
2.
J Med Microbiol ; 68(11): 1664-1670, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31553302

RESUMO

Purpose. To assess in vitro activities of nine antifungal agents (amphotericin B, fluconazole, voriconazole, itraconazole, posaconazole, caspofungin, micafungin, terbinafine and 5-flucytosine) against 93 strains of rare pathogenic fungi and the combined effects of drug combinations against several multidrug-resistant fungi.Methodology. The broth microdilution method M38-A3 and M27-A4 from the Clinical and Laboratory Standards Institute and the checkerboard method were performed in this study.Results. Low MICs for fluconazole were observed in moulds including Tritirachium oryzae, Exophiala attenuata and yeasts. MICs for amphotericin B>2 µg ml-1 were found among Aspergillus nidulans, Fusarium napiforme, Trichoderma longibrachiatum, Tritirachium oryzae, Cunninghamella bertholletiae, Cunninghamella phaeospora, Conidiobolus coronatus, Exophiala attenuata, Ochroconis mirabilis and Rhinocladiella basitona. Multidrug resistance was observed in Microascus spp., Lomentospora prolificans and Pythium insidiosum.Conclusion. Our study illustrated in vitro drug susceptibilities of some rare pathogenic fungi, which provide data to guide clinical treatment of fungal infections.


Assuntos
Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Micoses/microbiologia , Anfotericina B/farmacologia , Farmacorresistência Fúngica , Fluconazol/farmacologia , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Humanos , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Triazóis/farmacologia , Voriconazol/farmacologia
3.
Pestic Biochem Physiol ; 158: 18-24, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378355

RESUMO

Outbreaks of bitter rot were observed in three commercial apple orchards in Illinois despite best management efforts during the 2018 production season. Three isolates from symptomatic fruit from these orchards and two isolates from an orchard in South Carolina were identified to the species level using morphological tools and calmodulin, glyceraldehyde-3-phosphate dehydrogenase, and beta-tubulin gene sequences. The isolates from Illinois were identified as Colletotrichum siamense of the Colletotrichum gloeosporioides species complex and the ones from South Carolina as Colletotrichum fioriniae and Colletotrichum fructicola of the Colletotrichum acutatum and the C. gloeosporioides species complex, respectively. Two of the three C. siamense isolates from Illinois were resistant to azoxystrobin and thiophanate-methyl as determined in mycelial growth tests in vitro. EC50 values were >100 µg/ml for both fungicides. One isolate was only resistant to azoxystrobin. None of the isolates from South Carolina was resistant to either of the two compounds. All five isolates were sensitive to fludioxonil (EC50 values <0.1 µg/ml), propiconazole (EC50 values ranged from 0.15 to 0.36 µg/ml), and benzovindiflupyr (EC50 values ranged from <0.1 to 0.33 µg/ml). Resistance in C. siamense to azoxystrobin and thiophanate-methyl was confirmed in detached fruit studies using apples treated with label rates of registered product. Resistance to thiophanate-methyl in C. siamense was based on E198A mutation in b-tubulin gene, whereas resistance to azoxystrobin was based on G143A in cytochrome b (CYTB). One isolate resistant to azoxystrobin possessed no amino acid variation in CYTB. This study shows that quinone outside inhibitor fungicide resistance in Colletotrichum from apple has emerged and is being selected for in Illinois apple orchards by current spray strategies. Resistance monitoring may alert growers to potential threats, but the employment of molecular tools based on current knowledge of resistance mechanisms will provide incomplete results.


Assuntos
Colletotrichum/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Malus/microbiologia , Benzimidazóis/farmacologia , Colletotrichum/genética , Citocromos b/genética , Citocromos b/metabolismo , Dioxóis/farmacologia , Farmacorresistência Fúngica/genética , Frutas/microbiologia , Malus/genética , Norbornanos/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Estrobilurinas/farmacologia , Tiofanato/farmacologia , Triazóis/farmacologia
4.
Chem Pharm Bull (Tokyo) ; 67(8): 824-838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366832

RESUMO

We synthesized and evaluated novel 5-[2-(thiophen-2-yl)propan-2-yl]-4H-1,2,4-triazole derivatives as 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors. Optimization of the thiophene ring and the substituents on the 1,2,4-triazole ring produced 3,4-dicyclopropyl-5-{2-[3-fluoro-5-(trifluoromethyl)thiophen-2-yl]propan-2-yl}-4H-1,2,4-triazole monohydrochloride (9a), which showed potent and selective inhibitory activity against human 11ß-HSD1. Compound 9a was also metabolically stable against human and mouse liver microsomes. Oral administration of 9a to diabetic ob/ob mice lowered corticosterone levels in adipose tissue, and thereby reduced plasma glucose and insulin levels in a dose-dependent manner.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Triazóis/farmacologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Administração Oral , Animais , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Células HEK293 , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Obesos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/administração & dosagem , Triazóis/química
5.
Pestic Biochem Physiol ; 159: 91-97, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400790

RESUMO

The organophosphorus pesticide, triazophos (TAP) was banned to use in agriculture in several countries due to its high toxicity. However, TAP was still widely used and frequently detected in foods. Recently, many studies reported the endocrine-disrupting effect of pesticides, especially the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal axis. In this study, adult male Wistar rats were exposed to TAP at the dose of 0.164 and 1.64 mg/kg bodyweight (~1/500th and 1/50th of LD50) for 24 weeks and serum contents of hormones were measured. TAP exposure significantly reduced serum contents of adrenocorticotropic hormone, corticosterone and epinephrine in rats (p < .05), leading to the delay in glucose homeostasis during the insulin tolerance test and decrease in serum contents of total cholesterol, triglyceride and low density lipoprotein. Molecular docking results suggested TAP may be an antagonist of glucocorticoid receptor which decreased significantly in the liver of rats, resulting in the decreased expression of 11ß-hydroxysteroid dehydrogenase 1 and PEPCK1. This study revealed that TAP is a potential endocrine disruptor, especially in the hypothalamus-pituitary-adrenal system and may disturb the metabolism by affecting glucocorticoid receptor. This study provided new evidence about the toxicity of TAP and it was necessary to strictly control the usage of TAP in food.


Assuntos
Hipotálamo/efeitos dos fármacos , Organotiofosfatos/farmacologia , Praguicidas/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Triazóis/farmacologia , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Colesterol/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Simulação de Acoplamento Molecular , Ratos , Ratos Wistar , Triglicerídeos/metabolismo
6.
BMC Plant Biol ; 19(1): 342, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387526

RESUMO

BACKGROUND: GRAS are plant-specific transcription factors that play important roles in plant growth and development. Although the GRAS gene family has been studied in many plants, there has been little research on the GRAS genes of Tartary buckwheat (Fagopyrum tataricum), which is an important crop rich in rutin. The recently published whole genome sequence of Tartary buckwheat allows us to study the characteristics and expression patterns of the GRAS gene family in Tartary buckwheat at the genome-wide level. RESULTS: In this study, 47 GRAS genes of Tartary buckwheat were identified and divided into 10 subfamilies: LISCL, HAM, DELLA, SCR, PAT1, SCL4/7, LAS, SHR, SCL3, and DLT. FtGRAS genes were unevenly distributed on 8 chromosomes, and members of the same subfamily contained similar gene structures and motif compositions. Some FtGRAS genes may have been produced by gene duplications; tandem duplication contributed more to the expansion of the GRAS gene family in Tartary buckwheat. Real-time PCR showed that the transcription levels of FtGRAS were significantly different in different tissues and fruit development stages, implying that FtGRAS might have different functions. Furthermore, an increase in fruit weight was induced by exogenous paclobutrazol, and the transcription level of the DELLA subfamily member FtGRAS22 was significantly upregulated during the whole fruit development stage. Therefore, FtGRAS22 may be a potential target for molecular breeding or genetic editing. CONCLUSIONS: Collectively, this systematic analysis lays a foundation for further study of the functional characteristics of GRAS genes and for the improvement of Tartary buckwheat crops.


Assuntos
Fagopyrum/genética , Proteínas de Plantas/fisiologia , Fatores de Transcrição/fisiologia , Fagopyrum/crescimento & desenvolvimento , Fagopyrum/metabolismo , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Genoma de Planta , Família Multigênica , Filogenia , Desenvolvimento Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sintenia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triazóis/farmacologia
7.
Chem Biodivers ; 16(10): e1900377, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436917

RESUMO

The series of novel Mannich bases were synthesized and evaluated for their in vitro antibacterial activity against Gram-positive and Gram-negative bacterial strains. The results showed that all compounds were less active than the drugs used as reference, but some of them had moderate potency against Staphylococcus epidermidis ATCC 12228 and Bacillus subtilis ATCC 6633. The presence of a phenyl ring in the position 4 of piperazine seems to be necessary for antibacterial activity in this class of compounds.


Assuntos
Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bases de Mannich/química , Staphylococcus epidermidis/efeitos dos fármacos , Triazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Triazóis/síntese química , Triazóis/química
8.
J Agric Food Chem ; 67(33): 9220-9231, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31347838

RESUMO

Slow-release fungicide formulations (azoxystrobin, epoxiconazole, and tebuconazole) shaped as pellets and granules in a matrix of biodegradable poly(3-hydroxybutyrate) and natural fillers (clay, wood flour, and peat) were constructed. Infrared spectroscopy showed no formation of chemical bonds between components in the experimental formulations. The formulations of pesticides had antifungal activity against Fusarium verticillioides in vitro. A study of biodegradation of the experimental fungicide formulations in the soil showed that the degradation process was mainly influenced by the type of formulation without significant influence of the type of filler. More active destruction of the granules led to a more rapid accumulation of fungicides in the soil. The content of fungicides present in the soil as a result of degradation of the formulations and fungicide release was determined by their solubility. Thus, all formulations are able to function in the soil for a long time, ensuring gradual and sustained delivery of fungicides.


Assuntos
Argila/química , Preparações de Ação Retardada/química , Composição de Medicamentos/métodos , Fungicidas Industriais/química , Hidroxibutiratos/química , Poliésteres/química , Solo/química , Madeira/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Composição de Medicamentos/instrumentação , Compostos de Epóxi/química , Compostos de Epóxi/farmacologia , Fungicidas Industriais/farmacologia , Fusarium/efeitos dos fármacos , Cinética , Pirimidinas/química , Pirimidinas/farmacologia , Estrobilurinas/química , Estrobilurinas/farmacologia , Triazóis/química , Triazóis/farmacologia
9.
J Enzyme Inhib Med Chem ; 34(1): 1210-1217, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31286781

RESUMO

In this study, a series of 4,5-bis(substituted phenyl)-4H-1,2,4-triazol-3-amine compounds was designed, synthesised, and evaluated to determine their potential as anti-lung cancer agents. According to the results of screening of lung cancer cell lines A549, NCI-H460, and NCI-H23 in vitro, most of the synthesised compounds have potent cytotoxic activities with IC50 values ranging from 1.02 to 48.01 µM. Particularly, compound 4,5-bis(4-chlorophenyl)-4H-1,2,4-triazol-3-amine (BCTA) was the most potent anti-cancer agent, with IC50 values of 1.09, 2.01, and 3.28 µM against A549, NCI-H460, and NCI-H23 cells, respectively, meaning many-fold stronger anti-lung cancer activity than that of the chemotherapeutic agent 5-fluorouracil. We also explored the effects of BCTA on apoptosis in lung cancer cells by flow cytometry and western blotting. Our results indicated that BCTA induced apoptosis by upregulating proteins BAX, caspase 3, and PARP. Thus, the potential application of compound BCTA as a drug should be further examined.


Assuntos
Aminas/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Triazóis/síntese química , Triazóis/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Triazóis/química
10.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2213-2218, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359644

RESUMO

The aim of the study is to explore exogenous S3307 on alleviating low-temperature stress of coix seedlings. The coix cultivar, "No 5 Yiliao", was selected as the plant material, through nutrient solution cultivating in greenhouse, the effect of different S3307 concentrations(1, 3, 5, 7, 9 mg·L~(-1)) on coix seedlings traits and physiological indicators were explored under low-temperature stress. The results showed, under low-temperature 5 mg·L~(-1) S3307 could significantly increase coix seedlings stem diameter and biomass, which stem diameter and above-ground biomass, low-ground biomass separately were enhanced 11.90%, 13.59%, 10.99%. Leaf width and lateral root number separately were enhanced 7.63%, 37.52%. Meanwhile, addition of 5 mg·L~(-1) S3307 could significantly reduce relative conductivity and MDA, separately being reduced 23.33%, 17.42% compared to CKL. S3307 could also significantly increase soluble sugar and proline content, which leaf soluble sugar and proline content separately were enhanced 17.16%, 11.87%, which root soluble sugar and proline content separately were enhanced 20.00%, 33.42%. Additionally, S3307 could alleviate the cells destroy in ultra-structure level by improving cell membrane structure and chloroplast capsule layer structure. 5 mg·L~(-1) S3307 could enhance the low temperature tolerance of coix seedlings by regulating the growth and physiological indexes, and thus alleviate the damage caused by low-temperature to the coix seedlings.


Assuntos
Coix/efeitos dos fármacos , Temperatura Baixa , Plântula/efeitos dos fármacos , Estresse Fisiológico , Triazóis/farmacologia
11.
Molecules ; 24(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288497

RESUMO

Fungicide is used to control fungal disease by destroying and inhibiting the fungus or fungal spores that cause the disease. However, failure to deliver fungicide to the disease region leads to ineffectiveness in the disease control. Hence, in the present study, nanotechnology has enabled the fungicide active agents (hexaconazole) to be encapsulated into chitosan nanoparticles with the aim of developing a fungicide nanodelivery system that can transport them more effectively to the target cells (Ganoderma fungus). A pathogenic fungus, Ganoderma boninense (G. boninense), is destructive to oil palm whereby it can cause significant loss to oil palm plantations located in the Southeast Asian countries, especially Malaysia and Indonesia. In regard to this matter, a series of chitosan nanoparticles loaded with the fungicide, hexaconazole, was prepared using various concentrations of crosslinking agent sodium tripolyphosphate (TPP). The resulting particle size revealed that the increase of the TPP concentration produced smaller particles. In addition, the in vitro fungicide released at pH 5.5 demonstrated that the fungicide from the nanoparticles was released in a sustainable manner with a prolonged release time up to 86 h. On another note, the in vitro antifungal studies established that smaller particle size leads to lower half maximum effective concentration (EC50) value, which indicates higher antifungal activity against G. boninense.


Assuntos
Arecaceae/microbiologia , Quitosana/química , Portadores de Fármacos/química , Fungicidas Industriais/farmacologia , Ganoderma/efeitos dos fármacos , Nanopartículas/química , Doenças das Plantas/microbiologia , Triazóis/farmacologia , Reagentes para Ligações Cruzadas/química , Liberação Controlada de Fármacos , Cinética , Tamanho da Partícula , Polifosfatos/química
12.
J Agric Food Chem ; 67(30): 8303-8311, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31298535

RESUMO

Exposure to chiral pesticides poses many potential health risks. In this study, we examined the impacts of exposure to penconazole and its enantiomers on gut microbiota and metabolic profiles in mice. The relative abundance of microbiota in cecal content significantly changed following exposure to penconazole and its enantiomers. At the genus level, the relative abundances of seven gut microflora were altered following exposure to (-)-penconazole. Both (±)-penconazole and (+)-penconazole caused significant changes in the relative abundances of five gut microflora. In addition, targeted serum metabolomics analysis showed disturbed metabolic profiles following exposure. Respectively, (±)-penconazole, (+)-penconazole, and (-)-penconazole exposure significantly altered the relative levels of 29, 23, and 36 metabolites. In general, exposure to penconazole and its enantiomers caused disorders in gut microbiota and metabolic profiles of mice. The potential health risks of penconazole and its enantiomers now require further evaluation.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos/metabolismo , Praguicidas/química , Praguicidas/farmacologia , Triazóis/química , Triazóis/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Trato Gastrointestinal/microbiologia , Masculino , Camundongos Endogâmicos ICR , Filogenia , Estereoisomerismo
13.
Eur J Med Chem ; 179: 449-469, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271958

RESUMO

In this paper we describe the design and synthesis of bis(Het)Aryl-1,2,3-triazole quinuclidine α7R ligands using an efficient three-step sequence including a Suzuki-Miyaura cross coupling reaction with commercially available and home-made boron derivatives. The exploration of SAR required the preparation of uncommon boron derivatives. Forty final drugs were tested for their ability to bind the target and nine of them exhibited Ki values below nanomolar concentrations. The best scores were always obtained when the 5-phenyl-2-thiophenyl core was attached to the triazole. The selectivity of these compounds towards the nicotinic α4ß2 and serotoninergic 5HT3 receptors was assessed and their brain penetration was quantified by the preparation and in vivo evaluation of two [18F] radiolabelled derivatives. It can be expected from our results that some of these compounds will be suitable for further developments and will have effects on cognitive disorders.


Assuntos
Encéfalo/diagnóstico por imagem , Transtornos Cognitivos/tratamento farmacológico , Radioisótopos de Flúor/química , Marcação por Isótopo , Agonistas Nicotínicos/farmacologia , Tomografia por Emissão de Pósitrons , Quinuclidinas/farmacologia , Triazóis/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Animais , Encéfalo/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Relação Dose-Resposta a Droga , Ligantes , Estrutura Molecular , Agonistas Nicotínicos/síntese química , Agonistas Nicotínicos/química , Quinuclidinas/síntese química , Quinuclidinas/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química , Células Tumorais Cultivadas , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
14.
Food Chem ; 300: 125223, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31362157

RESUMO

The impact of fungicides mepanipyrim (Mep) and tetraconazole (Tetra) and their corresponding commercial formulations (Mep-Form and Tetra-Form) on the aroma composition of wines was assessed. Fungicide residues can affect the biotransformation of aroma precursors from grapes and/or the yeast metabolism. The results confirmed that both maximum residue levels (MRL and 2xMRL) of Mep promoted benzyl alcohol and 4-vinylguaiacol contents; while MRL and 2xMRL of Mep-Form promoted benzene derivatives (benzyl alcohol, benzaldehyde, and trans-isoeugenol), 2-phenylethanol and γ-nonalactone. The addition of Tetra (2xMRL) and Tetra-Form (MRL and 2xMRL) release higher contents of cis-3-hexen-1-ol and ethyl vanillate and affected yeast metabolism related to phenylacetaldehyde, 2-phenylethanol, methionol, capric acid, ethyl 2-methylbutyrate, ethyl isovalerate, ethyl monosuccionate, diethyl succinate and γ-butyrolactone production. Fungicide residues did not display higher variations in global odour activity values with respect to control wines, although some variations on the "floral", "fruity", "spicy" and "lactic" nuances could be sensed.


Assuntos
Clorobenzenos/farmacologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Vitis/efeitos dos fármacos , Compostos Orgânicos Voláteis/metabolismo , Vinho , Fermentação , Contaminação de Alimentos/análise , Frutas/química , Frutas/efeitos dos fármacos , Frutas/metabolismo , Fungicidas Industriais , Odorantes/análise , Vitis/química , Vitis/metabolismo , Compostos Orgânicos Voláteis/análise , Vinho/análise , Vinho/microbiologia , Leveduras/efeitos dos fármacos , Leveduras/metabolismo
15.
Plant Dis ; 103(9): 2271-2276, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31287371

RESUMO

Sensitivity monitoring of Venturia effusa, cause of pecan scab, has revealed insensitivity to fentin hydroxide and tebuconazole, but recent research indicates that the insensitivity to fentin hydroxide is not stable. A study was undertaken to determine if a fitness cost may be responsible for this instability. In this study, experiments were conducted to evaluate fitness components and phenotypic stability of insensitivity of V. effusa to fentin hydroxide and tebuconazole. Conidial production, conidial germination, microcolony growth, sensitivity to osmotic stress, and sensitivity to oxidative stress in the absence of fungicide were compared for isolates with differing sensitivities to both fungicides. Percent conidial germination decreased linearly with increasing fentin hydroxide insensitivity, and microcolony growth on 1.0 mM H2O2 decreased linearly with increasing tebuconazole insensitivity. Stability of resistance was assessed on concentrations of 1.0, 3.0, and 10 µg/ml of both fungicides prior to and after five transfers on non-fungicide-amended medium. Tebuconazole insensitivity was stable after transfers, but fentin hydroxide insensitivity on 1.0 and 3.0 µg/ml decreased significantly after transfers, indicating instability. Here we provide evidence that in V. effusa tebuconazole insensitivity is stable and fentin hydroxide insensitivity is not. These results suggest that fentin-hydroxide-resistant V. effusa isolates have reduced conidial viability compared with sensitive isolates, which may allow the population to regain sensitivity in the absence of this frequently used fungicide.


Assuntos
Ascomicetos , Farmacorresistência Fúngica , Compostos Orgânicos de Estanho , Triazóis , Ascomicetos/efeitos dos fármacos , Compostos Orgânicos de Estanho/farmacologia , Triazóis/farmacologia
16.
Eur J Med Chem ; 178: 433-445, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202991

RESUMO

Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (6g), a potent TRPV1 antagonist. In vitro, using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC50 = 0.075 µM) and only partially blocked acid activation of TRPV1. In vivo, 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs.


Assuntos
Desenho de Drogas , Indóis/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Triazóis/farmacologia , Animais , Relação Dose-Resposta a Droga , Indóis/administração & dosagem , Indóis/química , Masculino , Camundongos , Camundongos Endogâmicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Canais de Cátion TRPV/metabolismo , Triazóis/administração & dosagem , Triazóis/química
17.
Eur J Med Chem ; 177: 362-373, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158750

RESUMO

Inhibiting the decomposition of carbohydrates into glucose or promoting glucose conversion is considered to be an effective treatment for type 2 diabetes. Herein, a series of novel xanthone-triazole derivatives were designed, synthesized, and their α-glucosidase inhibitory activities and glucose uptake in HepG2 cells were investigated. Most of the compounds showed better inhibitory activities than the parental compound a (1,3-dihydroxyxanthone, IC50 = 160.8 µM) and 1-deoxynojirimycin (positive control, IC50 = 59.5 µM) towards α-glucosidase. Compound 5e was the most potent inhibitor, with IC50 value of 2.06 µM. The kinetics of enzyme inhibition showed that compounds 5e, 5g, 5h, 6c, 6d, 6g and 6h were noncompetitive inhibitors, and molecular docking results were consistent with the noncompetitive property that these compounds bind to allosteric sites away from the active site (Asp214, Glu276 and Asp349). On the other hand, the glucose uptake assays exhibited that compounds 5e, 6a, 6c and 7g displayed high activities in promoting the glucose uptake. The cytotoxicity assays showed that most compounds were low-toxic to human normal hepatocyte cell line (LO2). These novel xanthone triazole derivatives exhibited dual therapeutic effects of α-glucosidase inhibition and glucose uptake promotion, thus they could be use as antidiabetic agents for developing novel drugs against type 2 diabetes.


Assuntos
Glucose/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Triazóis/farmacologia , Xantonas/farmacologia , Sítios de Ligação , Desenho de Drogas , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/toxicidade , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/toxicidade , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/metabolismo , Triazóis/toxicidade , Xantonas/síntese química , Xantonas/metabolismo , Xantonas/toxicidade , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
18.
Eur J Med Chem ; 179: 182-195, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254920

RESUMO

A series of (1,2,4)triazole[4,3-a]pyridine (TZP) derivatives have been designed and synthesized. Compound 8d was identified as having the most potent inhibitory activity on NO release in response to lipopolysaccharide (LPS) stimulation and inhibition of the migration induced by MCP-1 protein on RAW264.7 macrophages. Based on the screening data, an immunofluorescence assay and a real-time qPCR assay were conducted, indicating that compound 8d suppressed NF-κB p65 translocation and expression of inflammatory genes by concanavalin A (Con A)-induced RAW264.7 macrophages. More importantly, 8d also exhibited potent efficacy, alleviating Con A-induced hepatitis by downregulating the levels of plasma alanine transaminase (ALT), aspartate transaminase (AST) and inflammatory infiltration in a mouse autoimmune hepatitis (AIH) model. In addition, the flow cytometry (FCM) data showed that compound 8d inhibited the accumulation of MDSCs in the liver of Con A-induced mice. These findings raise the possibility that compound 8d might serve as a potential agent for the treatment of AIH.


Assuntos
Concanavalina A/antagonistas & inibidores , Hepatite/tratamento farmacológico , Piridinas/farmacologia , Triazóis/farmacologia , Animais , Sobrevivência Celular , Células Cultivadas , Concanavalina A/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Desenho de Drogas , Feminino , Hepatite/metabolismo , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/biossíntese , Piridinas/síntese química , Piridinas/química , Células RAW 264.7 , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
19.
Artigo em Inglês | MEDLINE | ID: mdl-31177919

RESUMO

The fluorinated nucleoside dimers with a 1,2,3-triazole linkage are novel compounds within the field of bioorganic chemistry. We report on the synthesis and properties of two groups of nucleoside dimers analogs possessing a different arrangement of the 1,4-disubstituted 1,2,3-triazole linkage. Based on analysis of the 3JHH, 3JH1'C2, and 3JH1'C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. These compounds show moderate anticancer activity, with cytostatic studies in three different cancer cell lines.


Assuntos
Antineoplásicos/farmacologia , Nucleosídeos/farmacologia , Triazóis/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Click , Reação de Cicloadição , Dimerização , Floxuridina/análogos & derivados , Floxuridina/farmacologia , Humanos , Conformação Molecular , Nucleosídeos/química , Timidina/análogos & derivados , Timidina/farmacologia , Triazóis/química
20.
Environ Pollut ; 252(Pt A): 804-812, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31200206

RESUMO

6:2 fluorotelomer sulfonic acid (6:2 FTSA) is currently used as an alternative to perfluorooctanesulfonate (PFOS) and is widely detected in the environment. The uptake, translocation and biotransformation of 6:2 FTSA in pumpkin (Cucurbita maxima L.) were investigated by hydroponic exposure for the first time. The root concentration factor (RCF) of 6:2 FTSA was 2.6-24.2 times as high as those of perfluoroalkyl acids (PFAAs) of the same or much shorter carbon chain length, demonstrating much higher bioaccumulative ability of 6:2 FTSA in pumpkin roots. The translocation capability of 6:2 FTSA from root to shoot depended on its hydrophobicity. Six terminal perfluorocarboxylic acid (PFCA) metabolites, including perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluoropentanoic acid (PFPeA), perfluorobutanoic acid (PFBA), perfluoropropionic acid (PFPrA) and trifluoroacetic acid (TFA) were found in pumpkin roots and shoots. PFHpA was the primary metabolite in roots, while PFBA was the major product in shoots. 1-aminobenzotriazole (ABT), a cytochromes P450 (CYPs) suicide inhibitor, could decrease the concentrations of PFCA products with dose-dependent relationships in pumpkin tissues, implying the role of CYP enzymes involved in plant biotransformation of 6:2 FTSA. This study indicated that the application of 6:2 FTSA can lead to the occurrence of PFCAs (C2-C7) in plants.


Assuntos
Alcanossulfonatos/análise , Biodegradação Ambiental , Cucurbita/metabolismo , Ácidos Sulfônicos/análise , Alcanossulfonatos/química , Ácidos Alcanossulfônicos , Transporte Biológico , Biotransformação , Caproatos/análise , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Fluorcarbonetos/análise , Ácidos Heptanoicos/análise , Interações Hidrofóbicas e Hidrofílicas , Hidroponia , Ácidos Pentanoicos/análise , Ácidos Sulfônicos/química , Triazóis/farmacologia , Ácido Trifluoracético/análise
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