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Métodos Terapéuticos y Terapias MTCI
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1.
J Med Chem ; 62(4): 1875-1886, 2019 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-30688460

RESUMEN

The presence of lipopolysaccharide and emergence of drug resistance make the treatment of Gram-negative bacterial infections highly challenging. Herein, we present the synthesis and antibacterial activities of cholic acid-peptide conjugates (CAPs), demonstrating that valine-glycine dipeptide-derived CAP 3 is the most effective antimicrobial. Molecular dynamics simulations and structural analysis revealed that a precise intramolecular network of CAP 3 is maintained in the form of evolving edges, suggesting intramolecular connectivity. Further, we found high conformational rigidity in CAP 3 that confers maximum perturbations in bacterial membranes relative to other small molecules. Interestingly, CAP 3-coated catheters did not allow the formation of biofilms in mice, and treatment of wound infections with CAP 3 was able to clear the bacterial infection. Our results demonstrate that molecular conformation and internal connectivity are critical parameters to describe the antimicrobial nature of compounds, and the analysis presented here may serve as a general principle for the design of future antimicrobials.


Asunto(s)
Antibacterianos/uso terapéutico , Ácidos Cólicos/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Lipopolisacáridos/metabolismo , Péptidos/uso terapéutico , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/metabolismo , Animales , Antibacterianos/síntesis química , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Ácidos Cólicos/síntesis química , Ácidos Cólicos/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Escherichia coli/fisiología , Bacterias Gramnegativas/metabolismo , Bacterias Gramnegativas/fisiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/metabolismo , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Simulación de Dinámica Molecular , Péptidos/síntesis química , Péptidos/farmacología , Relación Estructura-Actividad
2.
J Biotechnol ; 254: 1-8, 2017 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-28602792

RESUMEN

In the present study, we compared the effects of Al3+ ions and alumina (Al2O3) nanoparticles (NPs) on growth and biochemical parameters of cabbage seedlings. The seedlings were treated with A=698.8µM Al3+ions and A1=101.8µM, A2=253.8µM, A3=507.7µM, A4=1.02mM, A5=2.17mM NPs of Al2O3 in 700mL Hoagland solution. The untreated seedlings were taken as control. It was observed that aluminium ions were phytotoxic and adversely affected seedling growth and biochemical parameters of the test crop with stunting of the stem growth, while lower doses of alumina NPs enhanced seedling growth, pigments, sugar and protein contents of cabbage (Brassica oleracea var. capitata) seedlings. Higher doses of alumina NPs adversely affected biochemical parameters and nitrate reductase activities of the treated seedlings. Alumina NPs induced activities of antioxidant enzymes viz. SOD, CAT and POX. Antioxidant enzyme activities increased under all treatments with maximum increase in the seedlings treated with aluminium ions and higher concentrations of alumina NPs. The lower amount of alumina NPs buttressed the metabolic processes of the test crop and appeared to mitigate the phytotoxic effects of aluminium ions.


Asunto(s)
Antioxidantes/farmacología , Brassica/crecimiento & desarrollo , Nanopartículas del Metal/química , Plantones/crecimiento & desarrollo , Óxido de Aluminio/química , Óxido de Aluminio/farmacología , Antioxidantes/química , Brassica/efectos de los fármacos , Brassica/metabolismo , Catalasa/metabolismo , Iones/farmacología , Plantones/efectos de los fármacos , Plantones/metabolismo , Superóxido Dismutasa/metabolismo
3.
PLoS One ; 9(4): e92400, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24705024

RESUMEN

Oxalate secretion was achieved in Pseudomonas fluorescens ATCC 13525 by incorporation of genes encoding Aspergillus niger oxaloacetate acetyl hydrolase (oah), Fomitopsis plaustris oxalate transporter (FpOAR) and Vitreoscilla hemoglobin (vgb) in various combinations. Pf (pKCN2) transformant containing oah alone accumulated 19 mM oxalic acid intracellularly but secreted 1.2 mM. However, in the presence of an artificial oxalate operon containing oah and FpOAR genes in plasmid pKCN4, Pf (pKCN4) secreted 13.6 mM oxalate in the medium while 3.6 mM remained inside. This transformant solubilized 509 µM of phosphorus from rock phosphate in alfisol which is 4.5 fold higher than the Pf (pKCN2) transformant. Genomic integrants of P. fluorescens (Pf int1 and Pf int2) containing artificial oxalate operon (plac-FpOAR-oah) and artificial oxalate gene cluster (plac-FpOAR-oah, vgb, egfp) secreted 4.8 mM and 5.4 mM oxalic acid, released 329 µM and 351 µM P, respectively, in alfisol. The integrants showed enhanced root colonization, improved growth and increased P content of Vigna radiata plants. This study demonstrates oxalic acid secretion in P. fluorescens by incorporation of an artificial operon constituted of genes for oxalate synthesis and transport, which imparts mineral phosphate solubilizing ability to the organism leading to enhanced growth and P content of V. radiata in alfisol soil.


Asunto(s)
Proteínas Bacterianas/genética , Hidrolasas/genética , Operón/genética , Ácido Oxálico/metabolismo , Fosfatos/metabolismo , Pseudomonas fluorescens , Hemoglobinas Truncadas/genética , Ácidos/farmacología , Aspergillus niger/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Coriolaceae/genética , Hidrolasas/metabolismo , Hidrólisis , Organismos Modificados Genéticamente , Fósforo/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/microbiología , Pseudomonas fluorescens/genética , Pseudomonas fluorescens/metabolismo
4.
Pharmacogn Rev ; 8(15): 61-6, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24600197

RESUMEN

In traditional system of medicine, the seeds of Strychnos potatorum Linn. (family: Loganiaceae) are used in the treatment of gonorrhea, leukorrhea leukeorrhea, gastropathy, bronchitis, chronic diarrhea, dysentery, renal and vesicle calculi, diabetes, conjunctivitis, scleritis, ulcers and other eye disease. An attempt has been made to highlight this medicinal seeds through phytochemical and pharmacological study. The present review deals with the phytochemical and pharmacological screening of therapeutic importance from Strychnos potatorum L., an important medicinal plant. This study includes the collective information of different medicinal uses of Strychnos potatorum. The generated data has provided the basis for its wide use as the therapeutant both in the traditional and folk medicines.

5.
Planta Med ; 77(17): 1958-64, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21728148

RESUMEN

Withania somnifera (L.) Dun. (Solanaceae), known as Indian ginseng, is one of the most popular medicinal plants in India. Considering the importance and common use of this plant, it is necessary to investigate its holistic metabolite profile. However, with existing analytical methods which are based on TLC and HPLC­UV (or MS), it is difficult to obtain information of the whole range of compounds appropriately. In this study, the metabolic characterization of Withania somnifera leaves, stems, and roots collected in six different regions in India was performed using ¹H NMR spectroscopy followed by principal component analysis (PCA) and hierarchical clustering analysis (HCA). Of the parts of Withania somnifera analyzed in this study, the leaf was found to have the widest range of metabolites, including amino acids, flavonoids, lipids, organic acids, phenylpropanoids, and sugars, as well as the main secondary metabolites of the plant, withanolides. The ¹H NMR spectra revealed the presence of two groups of withanolides: 4-OH and 5,6-epoxy withanolides (withaferin A-like steroids) and 5- OH and 6,7-epoxy withanolides (withanolides Alike steroids). The ratio of these two withanolides was found to be a key discriminating feature of Withania somnifera leaf samples from different origins.


Asunto(s)
Extractos Vegetales/química , Withania/química , Witanólidos/química , Análisis por Conglomerados , Geografía , India , Espectroscopía de Resonancia Magnética , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Tallos de la Planta/química , Tallos de la Planta/metabolismo , Plantas Medicinales/química , Plantas Medicinales/metabolismo , Análisis de Componente Principal , Withania/metabolismo , Witanólidos/aislamiento & purificación
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