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1.
Chem Biodivers ; 21(6): e202400408, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38441384

RESUMEN

To develop novel bacterial biofilm inhibiting agents, a series of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures were designed, synthesized, and characterized using 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. Meanwhile, their biological activities were evaluated, and the ensuing structure-activity relationships were discussed. The bioassay results showed the substantial antimicrobial efficacy exhibited by most of the compounds. Among them, compound A24 demonstrated a strong efficacy with an EC50 value of 7.8 µg/mL in vitro against the Xanthomonas oryzae pv. oryzicola (Xoc) pathogen, surpassing commercial agents thiodiazole copper (31.8 µg/mL) and bismerthiazol (43.3 µg/mL). Mechanistic investigations into its anti-Xoc properties revealed that compound A24 operates by increasing the permeability of bacterial cell membranes, inhibiting biofilm formation and cell motility, and inducing morphological changes in bacterial cells. Importantly, in vivo tests showed its excellent protective and curative effects on rice bacterial leaf streak. Besides, molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are key factors between the binding of A24 and AvrRxo1-ORF1. Therefore, these results suggest the utilization of 1,3,4-thiadiazole derivatives containing sulfonylpiperazine structures as a bacterial biofilm inhibiting agent, warranting further exploration in the realm of agrochemical development.


Asunto(s)
Antibacterianos , Biopelículas , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Tiadiazoles , Xanthomonas , Tiadiazoles/química , Tiadiazoles/farmacología , Tiadiazoles/síntesis química , Relación Estructura-Actividad , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Xanthomonas/efectos de los fármacos , Biopelículas/efectos de los fármacos , Piperazinas/farmacología , Piperazinas/química , Piperazinas/síntesis química , Estructura Molecular , Oryza/microbiología
2.
Plant Dis ; 2023 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-37172979

RESUMEN

Weizhi Xun and Changwang Wu contributed equally to this work In October 2020, bayberry (Myrica rubra (Lour.) S. et Zucc.) leaves that beginning to wither were collected in Wencheng County (N27°50', E120°03'). In the county, 4,120 ha of bayberry were planted, of which 58% were affected by the disease, and the severity of leaf disease per plant was 5 to25%. Bayberry leaves leaves were intensely green at first, then gradually turned yellow and brown,and completely withered. The leaves did not fall off at the beginning of the symptoms, but did fall after 1 to 2 months. To identify the pathogen, 50 diseased leaves with typical symptoms were collected from 10 diseased trees. Leaves with necrotic-tissue were firstly washed with sterilized water, and then tissue at the disease-/ healthy-tissuejunction removed with sterile surgical scissors. The tissues were soaked in 75% ethanol for 30 s, followed by 5% sodium hypochlorite solution for 3 to 4 min, rinsed with sterilized water 4 times, and placed on sterilized filter paper. The tissue was placed on PDA medium and cultured in an incubator at 25℃ (Nouri et al. 2019). After the colonies grew around the tissue, mycelia with the same morphology was selected and placed on fresh PDA. A pure culture of the pathogen was obtained after repeating the last process several times. The isolatedcolonies were white, with a round edge and a light-yellow back. Conidia were straight or slightly curved, with 3 to 4 septations. The internal transcribed spacer (ITS) regin translation elongation factor 1-α gene (TEF1-α), and beta-tubulin gene (ß-TUB)(Chaiwan et al. 2020; Li et al. 2021; Chen et al. 2020; Chen et al. 2018) of the two strains were amplified and sequenced, and the sequences were uploaded to Gen bank (GenBank accession number.ACCC 35162: ITS OP891011, TEF1-α OP903533, ß-TUB OP903531; ACCC 35163: ITS OP891012, ß-TUB OP903534, TEF1-α OP903532). BLAST alignment indicated that the ITS sequence of strain ACCC 35162 had 100% identity with NR_147549.1, the TEF sequence had 100% identity with MT552449.1, and the TUB sequence had 99.87% identity with KX895323.1; the ITS sequence of strain ACCC 35163 had 100% identity with NR_147549.1, the TEF sequence had 100% identity with MT552449.1, and the TUB sequence had 99.86% identity with KX895323.1. A Phylogenetic tree using maximum likelihood/rapid bootstrapping run on XSEDE based on the above three sequences inferred that the two strains were identical to P. kenyana (Miller et al. 2010). The strain was preserved in the Agricultural Culture Collection of China (Preservation numbers: ACCC 35162, ACCC 35163). Following Koch's rule, six healthy plants leaves were inoculated with conidial suspensions (106 conidia mL-1) and mycelial plugs (5 mm),and then placed in an artificial climate chamber (25℃, 90% humidity, 16-h light), sterile PDA and sterile water were used as blank controls. The same treatment was applied to fresh bayberry leaves under laboratory conditions, and brown spots were observed after three days. There were no symptoms in the control group. The experimental symptoms were similar to those in the field. Using the previous method, the same fungus was reisolated from the diseased leaves and again identified as P. kenyana. As far as we know, this is the first report causing disease on P. kenyana infecting bayberry in China, this disease seriously affected the yield and quality of bayberry and caused economic losses to farmers.

3.
Int J Mol Sci ; 24(14)2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37511033

RESUMEN

Pestalotiopsis sp. is an important class of plant pathogenic fungi that can infect a variety of crops. We have proved the pathogenicity of P. kenyana on bayberry leaves and caused bayberry blight. Phenazine-1-carboxylic acid (PCA) has the characteristics of high efficiency, low toxicity, and environmental friendliness, which can prevent fungal diseases on a variety of crops. In this study, the effect of PCA on the morphological, physiological, and molecular characteristics of P. kenyana has been investigated, and the potential antifungal mechanism of PCA against P. kenyana was also explored. We applied PCA on P. kenyana in vitro and in vivo to determine its inhibitory effect on PCA. It was found that PCA was highly efficient against P. kenyana, with EC50 around 2.32 µg/mL, and the in vivo effect was 57% at 14 µg/mL. The mechanism of PCA was preliminarily explored by transcriptomics technology. The results showed that after the treatment of PCA, 3613 differential genes were found, focusing on redox processes and various metabolic pathways. In addition, it can also cause mycelial development malformation, damage cell membranes, reduce mitochondrial membrane potential, and increase ROS levels. This result expanded the potential agricultural application of PCA and revealed the possible mechanism against P. kenyana.


Asunto(s)
Antifúngicos , Pestalotiopsis , Antifúngicos/farmacología , Hongos
4.
Int J Mol Sci ; 24(5)2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36902121

RESUMEN

Pesticides play an important role in crop disease and pest control. However, their irrational use leads to the emergence of drug resistance. Therefore, it is necessary to search for new pesticide-lead compounds with new structures. We designed and synthesized 33 novel pyrimidine derivatives containing sulfonate groups and evaluated their antibacterial and insecticidal activities. Results: Most of the synthesized compounds showed good antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), Pseudomonas syringae pv. actinidiae (Psa) and Ralstonia solanacearum (Rs), and certain insecticidal activity. A5, A31 and A33 showed strong antibacterial activity against Xoo, with EC50 values of 4.24, 6.77 and 9.35 µg/mL, respectively. Compounds A1, A3, A5 and A33 showed remarkable activity against Xac (EC50 was 79.02, 82.28, 70.80 and 44.11 µg/mL, respectively). In addition, A5 could significantly improve the defense enzyme (superoxide dismutase, peroxidase, phenylalanine ammonia-lyase and catalase) activity of plants against pathogens and thus improve the disease resistance of plants. Moreover, a few compounds also showed good insecticidal activity against Plutella xylostella and Myzus persicae. The results of this study provide insight into the development of new broad-spectrum pesticides.


Asunto(s)
Antibacterianos , Ésteres , Plaguicidas , Pirimidinas , Sulfuros , Alcanosulfonatos , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Ésteres/síntesis química , Ésteres/química , Ésteres/farmacología , Pruebas de Sensibilidad Microbiana , Oryza/microbiología , Plaguicidas/síntesis química , Plaguicidas/química , Plaguicidas/farmacología , Enfermedades de las Plantas/microbiología , Pirimidinas/síntesis química , Pirimidinas/química , Pirimidinas/farmacología , Sulfuros/síntesis química , Sulfuros/química , Sulfuros/farmacología , Xanthomonas/efectos de los fármacos
5.
Int J Mol Sci ; 24(12)2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37373374

RESUMEN

Blister blight (BB) disease is caused by the obligate biotrophic fungal pathogen Exobasidium vexans Massee and seriously affects the yield and quality of Camellia sinensis. The use of chemical pesticides on tea leaves substantially increases the toxic risks of tea consumption. Botanic fungicide isobavachalcone (IBC) has the potential to control fungal diseases on many crops but has not been used on tea plants. In this study, the field control effects of IBC were evaluated by comparison and in combination with natural elicitor chitosan oligosaccharides (COSs) and the chemical pesticide pyraclostrobin (Py), and the preliminary action mode of IBC was also investigated. The bioassay results for IBC or its combination with COSs showed a remarkable control effect against BB (61.72% and 70.46%). IBC, like COSs, could improve the disease resistance of tea plants by enhancing the activity of tea-plant-related defense enzymes, including polyphenol oxidase (PPO), catalase (CAT), phenylalanine aminolase (PAL), peroxidase (POD), superoxide dismutase (SOD), ß-1,3-glucanase (Glu), and chitinase enzymes. The fungal community structure and diversity of the diseased tea leaves were examined using Illumina MiSeq sequencing of the internal transcribed spacer (ITS) region of the ribosomal rDNA genes. It was obvious that IBC could significantly alter the species' richness and the diversity of the fungal community in affected plant sites. This study broadens the application range of IBC and provides an important strategy for the control of BB disease.


Asunto(s)
Camellia sinensis , Chalconas , Camellia sinensis/genética , Resistencia a la Enfermedad/genética , Chalconas/farmacología , , Enfermedades de las Plantas/microbiología
6.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36769220

RESUMEN

Anti-virulence strategies are attractive and interesting strategies for controlling bacterial diseases because virulence factors are fundamental to the infection process of numerous serious phytopathogenics. To extend the novel anti-virulence agents, a series of dehydroabietic acid (DAA) derivatives decorated with amino alcohol unit were semi-synthesized based on structural modification of the renewable natural DAA and evaluated for their antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). Compound 2b showed the most promising antibacterial activity against Xoo with an EC50 of 2.7 µg mL-1. Furthermore, compound 2b demonstrated remarkable control effectiveness against bacterial leaf blight (BLB) in rice, with values of 48.6% and 61.4% for curative and protective activities. In addition, antibacterial behavior suggested that compound 2b could suppress various virulence factors, including EPS, biofilm, swimming motility, and flagella. Therefore, the current study provided promising lead compounds for novel bactericides discovery by inhibiting bacterial virulence factors.


Asunto(s)
Oryza , Xanthomonas , Oxadiazoles/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/química , Oryza/microbiología , Factores de Virulencia , Enfermedades de las Plantas/microbiología
7.
Int J Mol Sci ; 23(10)2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35628277

RESUMEN

Chitosan oligosaccharide (COS) plays an important role in the growth and development of tea plants. However, responses in tea plants trigged by COS have not been thoroughly investigated. In this study, we integrated transcriptomics and metabolomics analysis to understand the mechanisms of chitosan-induced tea quality improvement and growth promotion. The combined analysis revealed an obvious link between the flourishing development of the tea plant and the presence of COS. It obviously regulated the growth and development of the tea and the metabolomic process. The chlorophyll, soluble sugar, and amino acid content in the tea leaves was increased. The phytohormones, carbohydrates, and amino acid levels were zoomed-in in both transcript and metabolomics analyses compared to the control. The expression of the genes related to phytohormones transduction, carbon fixation, and amino acid metabolism during the growth and development of tea plants were significantly upregulated. Our findings indicated that alerted transcriptomic and metabolic responses occurring with the application of COS could cause efficiency in substrates in pivotal pathways and hence, elicited plant growth.


Asunto(s)
Camellia sinensis , Quitosano , Aminoácidos/metabolismo , Camellia sinensis/metabolismo , Quitosano/metabolismo , Regulación de la Expresión Génica de las Plantas , Metabolómica , Oligosacáridos/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Té/genética , Té/metabolismo , Transcriptoma
8.
Molecules ; 25(8)2020 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-32290634

RESUMEN

A series of new N-phenylacetamide derivatives containing 4-arylthiazole moieties was designed and synthesized by introducing the thiazole moiety into the amide scaffold. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Their in vitro antibacterial activities were evaluated against three kinds of bacteria-Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac) and X.oryzae pv. oryzicola (Xoc)-showing promising results. The minimum 50% effective concentration (EC50) value of N-(4-((4-(4-fluoro-phenyl)thiazol-2-yl)amino)phenyl)acetamide (A1) is 156.7 µM, which is superior to bismerthiazol (230.5 µM) and thiodiazole copper (545.2 µM). A scanning electron microscopy (SEM) investigation has confirmed that compound A1 could cause cell membrane rupture of Xoo. In addition, the nematicidal activity of the compounds against Meloidogyne incognita (M. incognita) was also tested, and compound A23 displayed excellent nematicidal activity, with mortality of 100% and 53.2% at 500 µg/mL and 100 µg/mL after 24 h of treatment, respectively. The preliminary structure-activity relationship (SAR) studies of these compounds are also briefly described. These results demonstrated that phenylacetamide derivatives may be considered as potential leads in the design of antibacterial agents.


Asunto(s)
Antibacterianos/farmacología , Antinematodos/farmacología , Enfermedades de las Plantas/prevención & control , Tylenchoidea/efectos de los fármacos , Xanthomonas axonopodis/efectos de los fármacos , Xanthomonas/efectos de los fármacos , Acetanilidas/síntesis química , Acetanilidas/farmacología , Animales , Antibacterianos/síntesis química , Antinematodos/síntesis química , Diseño de Fármacos , Espectroscopía de Resonancia Magnética , Oryza/microbiología , Oxadiazoles/química , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/farmacología
9.
Molecules ; 25(7)2020 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-32218317

RESUMEN

Abstract: In order to discover new lead compounds with high antibacterial activity, a series of new derivatives were designed and synthesized by introducing a sulfonate or carboxylate moiety into the 1,3,4-oxadiazole structure. Antibacterial activity against two phytopathogens, Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac), was assayed in vitro. The preliminary results indicated that ten compounds including 4a-1-4a-4 and 4a-11-4a-16 had good antibacterial activity against Xoo, with EC50 values ranging from 50.1-112.5 µM, which was better than those of Bismerthiazol (253.5 µM) and Thiodiazole copper (467.4 µM). Meanwhile, 4a-1, 4a-2, 4a-3 and 4a-4 demonstrated good inhibitory effect against Xanthomonas axonopodis pv. citri with EC50 values around 95.8-155.2 µM which were better than those of bismerthiazol (274.3 µM) and thiodiazole copper (406.3 µM). In addition, in vivo protection activity of compound 4a-2 and 4a-3 against rice bacterial leaf blight was 68.6% and 62.3%, respectively, which were better than bismerthiazol (49.6%) and thiodiazole copper (42.2%). Curative activity of compound 4a-2 and 4a-3 against rice bacterial leaf blight was 62.3% and 56.0%, which were better than bismerthiazol (42.9%) and thiodiazole copper (36.1%). Through scanning electron microscopy (SEM) analysis, it was observed that compound 4a-2 caused the cell membrane of Xanthomonas oryzae pv. oryzae ruptured or deformed. The present results indicated novel derivatives of 5-phenyl sulfonate methyl 1,3,4-oxadiazole might be potential antibacterial agents.


Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Ácidos Carboxílicos/química , Oxadiazoles/síntesis química , Oxadiazoles/farmacología , Ácidos Sulfónicos/química , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Oryza/efectos de los fármacos , Oryza/microbiología , Relación Estructura-Actividad , Xanthomonas/efectos de los fármacos , Xanthomonas/ultraestructura , Xanthomonas axonopodis/efectos de los fármacos
10.
J Environ Sci Health B ; 54(10): 858-865, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31264923

RESUMEN

Pheromones can be used as leafhopper attractants. However, commercial pheromone products, such as the Ingle lure, have certain limitations, including poor persistence in the field. In this study, (E)-2-hexenal, (Z)-3-hexen-1-ol, (Z)-3-hexenyl acetate, (E)-ocimene, linalool, and geraniol were selected and behaviorally tested as potential leafhopper attractants. Y-tube olfactometer tests showed that the C2 formulation was more effective than other formulations. In tea field trials, the number of leafhoppers caught by sticky board traps baited with C2 lures was greater than that caught by treatment. The number of leafhoppers attracted by the C2 lures was greater than that attracted by the commercial Ingle lures. Additionally, the total amount of active C2 components on lures was greater than that of the active components on the lure after 14 days. Thus, the results indicated that the C2 formulation may attract leafhoppers and have a greater persistence than other formulations in tea field.


Asunto(s)
Hemípteros/efectos de los fármacos , Feromonas/farmacología , Monoterpenos Acíclicos/farmacología , Aldehídos/farmacología , Animales , Camellia sinensis , China , Evaluación Preclínica de Medicamentos
11.
Clin Lab ; 64(4): 627-637, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29739092

RESUMEN

BACKGROUND: To study the clinical and genetic features from a Chinese child with SATB2-associated syndrome (SAS) and review of literature. METHODS: The girl, 2 years 3 months old, is admitted to the Department of Pediatric Rehabilitation in our hospital. This patient has mental retardation, language development disorder, cleft palate II0, micrognathia, malocclusion, irritability and bilateral oblique palpebral fissure as a clinical manifestation and is treated for 3 months. RESULTS: Gesell Development Scale (GDS) evaluation displays the patient's action capacity: gross motor 13.4, DQ 41%; fine motor 14.1, DQ 44%; adaptive behavior: DA 15.2, DQ 47%; speech capacity: DA 8.8; DQ 27%; person capacity: DA 11.7, DQ, 36%. Bayley Scale evaluation displays MDI < 50 and PDI < 50. Sleep EEG showed bilateral frontal pole - frontal - central - anterior temporal area presents in sharp wave, sharp and slow wave synchronization issue. A brain MRI showed that signal T2 is strengthened in the internal capsule hind leg. Flake T2FLATR high signal can been showed in the periventricular area of the parietal lobe in bilateral hemisphere. Molecular studies showed the patient carries a de novo nonsense mutation c.1285G>A (p.R429X) in SATB2. CONCLUSIONS: SATB2 mutation is not detected in the parents of the subjects. This study is important to further study the clinical features of SATB2-associated syndrome and to enlarge the SATB2 mutation spectrum.


Asunto(s)
Anomalías Múltiples/genética , Codón sin Sentido , Discapacidades del Desarrollo/genética , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Factores de Transcripción/genética , Secuencia de Bases , Preescolar , China , Análisis Mutacional de ADN , Femenino , Humanos , Síndrome
12.
Bioorg Med Chem Lett ; 27(17): 4096-4100, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28751145

RESUMEN

In this study, we report the synthesis and antiviral activity of trans-ferulic acid derivatives containing acylhydrazone moiety. Biological tests demonstrated that most target compounds showed potent antiviral activity against tobacco mosaic virus (TMV). Compound D4 showed remarkable inactivating activity with EC50 value of 36.59µg/mL, which was obviously superior to ribavirin (126.05µg/mL). Molecular docking results revealed that compound D4 exhibited the optimal combining capacity with five hydrogen bonds to different amino-acid residues of TMV coat protein (TMV-CP). Docking results were consistent with the inactivating activity of target compounds against TMV.


Asunto(s)
Antivirales/farmacología , Ácidos Cumáricos/farmacología , Hidrazonas/farmacología , Simulación del Acoplamiento Molecular , Virus del Mosaico del Tabaco/efectos de los fármacos , Antivirales/síntesis química , Antivirales/química , Ácidos Cumáricos/síntesis química , Ácidos Cumáricos/química , Relación Dosis-Respuesta a Droga , Hidrazonas/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad
13.
Clin Lab ; 63(7): 1153-1162, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28792689

RESUMEN

BACKGROUND: Tau protein is s specific protein expressed by neurons in the central nervous system. Elevated serum Tau protein is associated with many diseases of the central nervous system. The serum Tau protein level in neonates with hypoxic ischemic encephalopathy (HIE) is still poorly understood. METHODS: Forty-one human neonates with HIE and thirty-five healthy neonates (control group) within 24 hours after birth were studied. Tau protein in serum was detected by enzyme-linked immunosorbent assay. Neurological outcome was assessed at 9 months of age according to the Gesell developmental scale. RESULTS: Tau protein in serum was significantly higher in the HIE group than in the control group (p < 0.01), in neonates with severe HIE than neonates with moderate HIE (p < 0.01), and in infants with neurodevelopmental retardation compared with those with normal neurodevelopment (p < 0.01). The result of this study showed an obvious negative correlation between the serum Tau protein level and development quotients of neonates with HIE (rs = -0.6172, p < 0.01). Receiver operator characteristic curve analysis showed that Tau protein (cutoff value 933.04 pg/mL) was a predictor of neurodevelopmental retardation outcome (AUC value = 0.860 (95% CI: 0.736 - 0.983, p < 0.01), sensitivity 100%, specificity 70.8%). CONCLUSIONS: Serum Tau protein level within 24 hours after birth can be used as a marker for the early diagnosis of neonatal HIE and predicting neurodevelopmental outcomes.


Asunto(s)
Hipoxia-Isquemia Encefálica/sangre , Proteínas tau/sangre , Biomarcadores/sangre , Proteínas Sanguíneas , Humanos , Recién Nacido , Sensibilidad y Especificidad
14.
Bioorg Med Chem Lett ; 26(1): 168-73, 2016 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-26598463

RESUMEN

A series of novel malonate derivatives containing quinazolin-4(3H)-one moiety were synthesized and evaluated for their antiviral activities against cucumber mosaic virus (CMV). Results indicated that the title compounds exhibited good antiviral activities. Notably, compounds g15, g16, g17, and g18 exhibited excellent curative activities in vivo against CMV, with 50% effective concentration (EC50) values of 208.36, 153.78, 181.47, and 164.72µg/mL, respectively, which were better than that of Ningnanmycin (256.35µg/mL) and Ribavirin (523.34µg/mL). Moreover, statistically valid three-dimensional quantitative structure-activity relationship (3D-QSAR) models with good correlation and predictive power were obtained with comparative molecular field analysis (CoMFA) steric and electrostatic fields (r(2)=0.990, q(2)=0.577) and comparative molecular similarity indices analysis (CoMSIA) with combined steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (r(2)=0.977, q(2)=0.516), respectively. Based on those models, compound g25 was designed, synthesized, and showed better curative activity (146.30µg/mL) than that of compound g16. The interaction of between cucumber mosaic virus coat protein (CMV CP) and g25 with 1:1.83 ratio is typically spontaneous and exothermic with micromole binding affinity by isothermal titration calorimetry (ITC) and fluorescence spectroscopy investigation.


Asunto(s)
Antivirales/farmacología , Cucumovirus/efectos de los fármacos , Malonatos/farmacología , Relación Estructura-Actividad Cuantitativa , Quinazolinonas/farmacología , Antivirales/síntesis química , Antivirales/química , Relación Dosis-Respuesta a Droga , Malonatos/síntesis química , Malonatos/química , Pruebas de Sensibilidad Microbiana , Quinazolinonas/química
15.
Int J Mol Sci ; 17(3): 252, 2016 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-26927077

RESUMEN

Studies of the targets of anti-viral compounds are hot topics in the field of pesticide research. Various efficient anti-TMV (Tobacco Mosaic Virus) compounds, such as Ningnanmycin (NNM), Antofine (ATF), Dufulin (DFL) and Bingqingxiao (BQX) are available. However, the mechanisms of the action of these compounds on targets remain unclear. To further study the mechanism of the action of the anti-TMV inhibitors, the TMV coat protein (TMV CP) was expressed and self-assembled into four-layer aggregate disks in vitro, which could be reassembled into infectious virus particles with TMV RNA. The interactions between the anti-TMV compounds and the TMV CP disk were analyzed by size exclusion chromatography, isothermal titration calorimetry and native-polyacrylamide gel electrophoresis methods. The results revealed that assembly of the four-layer aggregate disk was inhibited by NNM; it changed the four-layer aggregate disk into trimers, and affected the regular assembly of TMV CP and TMV RNA. The four-layer aggregate disk of TMV CP was little inhibited by ATF, DFL and BQX. Our results provide original data, as well as new strategies and methods, for research on the mechanism of action of anti-viral drugs.


Asunto(s)
Antivirales/farmacología , Benzotiazoles/farmacología , Proteínas de la Cápside/antagonistas & inhibidores , Citidina/análogos & derivados , Indoles/farmacología , Fenantrolinas/farmacología , Virus del Mosaico del Tabaco/efectos de los fármacos , Secuencia de Aminoácidos , Proteínas de la Cápside/química , Proteínas de la Cápside/metabolismo , Citidina/farmacología , Datos de Secuencia Molecular , Unión Proteica , Virus del Mosaico del Tabaco/metabolismo
16.
Molecules ; 22(1)2016 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-28042864

RESUMEN

Sulfones are one of the most important classes of agricultural fungicides. To discover new lead compounds with high antibacterial activity, a series of new sulfone derivatives were designed and synthesized by introducing the aroxymethyl moiety into the scaffold of 1,3,4-oxadiazole/thiadiazole sulfones. Antibacterial activities against three phytopathogens (Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, Xanthomonas axonopodis pv. citri.) were assayed in vitro. As compared to the control of commercial fungicides and some reported sulfone fungicides, seven compounds 5I-1-5I-7 exerted remarkably higher activities with EC50 values ranging from 0.45-1.86 µg/mL against X. oryzae and 1.97-20.15 µg/mL against R. solanacearum. Exhilaratingly, 5I-1, 5I-2 and 5I-4 displayed significant in vivo activity against X. oryzae with protective effect of 90.4%, 77.7%, and 81.1% at 200 µg/mL, respectively, much higher than that exhibited by Bismerthiazol (25.6%) and Thiadiazole-copper (32.0%). And the differential phytotoxicity of active derivatives was preliminarily checked. The results demonstrated that derivative of 2-aroxymethyl-1,3,4-oxadiazole/thiadiazole sulfone can serve as potential alternative bactericides for the management of plant bacterial diseases.


Asunto(s)
Antibacterianos/farmacología , Oxadiazoles/química , Ralstonia solanacearum/efectos de los fármacos , Sulfonas/síntesis química , Sulfonas/farmacología , Tiadiazoles/química , Xanthomonas/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Enfermedades de las Plantas/microbiología , Relación Estructura-Actividad , Sulfonas/química
17.
Chemistry ; 21(28): 9984-7, 2015 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-26037373

RESUMEN

The reaction mechanism of the γ-carbon addition of enal to imine under oxidative N-heterocyclic carbene catalysis is studied experimentally. The oxidation, γ-carbon deprotonation, and nucleophilic addition of γ-carbon to imine were found to be facile steps. The results of our study also provide highly enantioselective access to tricyclic sulfonyl amides that exhibit interesting antimicrobial activities against X. oryzae, a bacterium that causes bacterial disease in rice growing.


Asunto(s)
Aldehídos/química , Antiinfecciosos/química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Iminas/química , Metano/análogos & derivados , Oryza/química , Sulfonamidas/química , Sulfonamidas/farmacología , Metano/química , Estructura Molecular , Oxidación-Reducción , Estereoisomerismo
18.
Bioorg Med Chem Lett ; 25(3): 481-4, 2015 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-25563889

RESUMEN

In this study, a series of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt caused by Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum) via the turbidimeter test in vitro. Antibacterial bioassays indicated that most compounds demonstrated appreciable antibacterial bioactivities against Xoo and R. solanacearum. Among the title compounds, compound 4i demonstrated the best inhibitory effect against Xoo and R. solanacearum with half-maximal effective concentration (EC50) values of 14.69 and 15.14µg/mL, respectively, which were even better than those of commercial agents Bismerthiazol and Thiodiazole Copper. In vivo antibacterial activities tests under greenhouse conditions revealed that the control efficiency of compound 4i against rice bacterial leaf blight and tobacco bacterial wilt were better than those of Bismerthiazol and Thiodiazole Copper. Meanwhile, field trials also indicated that compound 4i demonstrated appreciable control efficiency against rice bacterial leaf blight and tomato bacterial wilt.


Asunto(s)
Antibacterianos/química , Oryza/microbiología , Oxadiazoles/química , Solanum lycopersicum/microbiología , Tiadiazoles/química , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Oxadiazoles/farmacología , Enfermedades de las Plantas/microbiología , Hojas de la Planta/microbiología , Ralstonia solanacearum/efectos de los fármacos , Ralstonia solanacearum/aislamiento & purificación , Relación Estructura-Actividad , Tiadiazoles/farmacología , Xanthomonas/efectos de los fármacos , Xanthomonas/aislamiento & purificación
19.
Chirality ; 27(3): 262-7, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25644775

RESUMEN

The stereoselective degradation of indoxacarb enriched with (+)-S-indoxacarb (S/R:70/30) was investigated in three typical green teas. A convenient and precise chiral method was developed and validated for measuring indoxacarb enantiomers in green tea. The developed method was based on high-performance liquid chromatography coupled with tandem mass spectrometry using a Chiralpak IC column. The stereoselective degradation of indoxacarb enantiomers showed that the (+)-S-enantiomer dissipated faster than the (-)-R-enantiomer in all three typical tea farms. However, no enantiomerization was observed after applying pure (+)-S-indoxacarb. Residues on tea plant of the active ingredient (+)-S-indoxacarb from suspension concentrate (SC) was more persistent than that from emulsifiable concentrate (EC).


Asunto(s)
Oxazinas/química , Té/química , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Estereoisomerismo , Espectrometría de Masas en Tándem
20.
Front Pediatr ; 12: 1288853, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766393

RESUMEN

Hypothermia has been widely used to treat moderate to severe neonatal hypoxic-ischemic encephalopathy (HIE), yet evaluating the effects of hypothermia relies on clinical neurology, neuroimaging, amplitude-integrated electroencephalography, and follow-up data on patient outcomes. Biomarkers of brain injury have been considered for estimating the effects of hypothermia. Proteins specific to the central nervous system (CNS) are components of nervous tissue, and once the CNS is damaged, these proteins are released into biofluids (cerebrospinal fluid, blood, urine, tears, saliva), and they can be used as markers of brain damage. Clinical reports have shown that CNS-specific marker proteins (CNSPs) were early expressed in biofluids after brain damage and formed unique biochemical profiles. As a result, these markers may serve as an indicator for screening brain injury in infants, monitoring disease progression, identifying damage region of brain, and assessing the efficacy of neuroprotective measures. In clinical work, we have found that there are few reports on using CNSPs as biological signals in hypothermia for neonatal HIE. The aim of this article is to review the classification, origin, biochemical composition, and physiological function of CNSPs with changes in their expression levels after hypothermia for neonatal HIE. Hopefully, this review will improve the awareness of CNSPs among pediatricians, and encourage future studies exploring the mechanisms behind the effects of hypothermia on these CNSPs, in order to reduce the adverse outcome of neonatal HIE.

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