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1.
Plant Commun ; 5(7): 100891, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38561965

RESUMEN

Plants that grow in extreme environments represent unique sources of stress-resistance genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic evergreen broadleaf shrub native to semi-arid and desert regions; however, its drought-tolerance mechanisms remain poorly understood. Here, we report the assembly of a reference-grade genome for A. mongolicus, describe its evolutionary history within the legume family, and examine its drought-tolerance mechanisms. The assembled genome is 843.07 Mb in length, with 98.7% of the sequences successfully anchored to the nine chromosomes of A. mongolicus. The genome is predicted to contain 47 611 protein-coding genes, and 70.71% of the genome is composed of repetitive sequences; these are dominated by transposable elements, particularly long-terminal-repeat retrotransposons. Evolutionary analyses revealed two whole-genome duplication (WGD) events at 130 and 58 million years ago (mya) that are shared by the genus Ammopiptanthus and other legumes, but no species-specific WGDs were found within this genus. Ancestral genome reconstruction revealed that the A. mongolicus genome has undergone fewer rearrangements than other genomes in the legume family, confirming its status as a "relict plant". Transcriptomic analyses demonstrated that genes involved in cuticular wax biosynthesis and transport are highly expressed, both under normal conditions and in response to polyethylene glycol-induced dehydration. Significant induction of genes related to ethylene biosynthesis and signaling was also observed in leaves under dehydration stress, suggesting that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Ectopic expression of AmERF2, an ethylene response factor unique to A. mongolicus, can markedly increase the drought tolerance of transgenic Arabidopsis thaliana plants, demonstrating the potential for application of A. mongolicus genes in crop improvement.


Asunto(s)
Sequías , Fabaceae , Genoma de Planta , Fabaceae/genética , Fabaceae/fisiología , Estrés Fisiológico/genética , Evolución Molecular , Regulación de la Expresión Génica de las Plantas , Filogenia
2.
Chemistry ; 30(2): e202302708, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-37732540

RESUMEN

Vinyl ethers are valuable synthetic intermediates which are also found as natural products, including aflatoxins, rifamycins and plasmalogens. The latter are ubiquitous phospholipids in human cells and contain a vinyl ether moiety with specifically Z configuration. Although numerous methods are available for synthesis of vinyl ethers, there is a lack of methods for obtaining Z isomers of molecules of the type RCH=CHOR' that are applicable to plasmalogens. A variant of the Peterson reaction is described that generates such molecules with very high stereoselectivity (Z/E ratio: 99 : 1). (R,R)/(S,S)-1-alkoxy-2-hydroxyalkylsilanes were synthesized from 1-trimethylsilylalkynes by a sequence of reduction with di-isobutylaluminium hydride to a (Z)-1-trimethylsilylalkene, epoxidation of the alkene to a 2-trimethylsilyl-3-substituted epoxide and regioselective, boron-trifluoride catalyzed ring-opening of the epoxide by reaction with an alcohol. Conversion of the (R,R)/(S,S)-1-alkoxy-2-hydroxyalkylsilanes to vinyl ethers (RCH=CHOR') was achieved under basic conditions as in a standard Peterson reaction. However, near exclusive formation of a Z vinyl ether was only achieved when the reaction was performed using potassium hydride in the non-polar solvent α,α,α-trifluorotoluene, more polar solvents giving increasing amounts of the E isomer. The sequence described embraces a variety of substituents and precursors, proceeds in overall high yield and is readily scalable.

3.
Chem Commun (Camb) ; 59(89): 13333-13335, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37867450

RESUMEN

A new benzyl-type protecting group (1,4-dimethoxynaphthalene-2-methyl, 'DIMON') for hydroxyl functions can be selectively removed under oxidative conditions without damaging polyunsaturated fatty acyl groups. Its application is shown by the first synthesis of an ether (plasmanyl) phospholipid containing the docosa-(4Z,7Z,10Z,13Z,16Z,19Z)-hexaenoyl group.


Asunto(s)
Lípidos , Lípidos/química
4.
Molecules ; 26(6)2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33808840

RESUMEN

α-l-arabinofuranosidase is a subfamily of glycosidases involved in the hydrolysis of l-arabinofuranosidic bonds, especially in those of the terminal non-reducing arabinofuranosyl residues of glycosides, from which efficient glycoside hydrolases can be screened for the transformation of ginsenosides. In this study, the ginsenoside Rc-hydrolyzing α-l-arabinofuranosidase gene, BsAbfA, was cloned from Bacilus subtilis, and its codons were optimized for efficient expression in E. coli BL21 (DE3). The recombinant protein BsAbfA fused with an N-terminal His-tag was overexpressed and purified, and then subjected to enzymatic characterization. Site-directed mutagenesis of BsAbfA was performed to verify the catalytic site, and the molecular mechanism of BsAbfA catalyzing ginsenoside Rc was analyzed by molecular docking, using the homology model of sequence alignment with other ß-glycosidases. The results show that the purified BsAbfA had a specific activity of 32.6 U/mg. Under optimal conditions (pH 5, 40 °C), the kinetic parameters Km of BsAbfA for pNP-α-Araf and ginsenoside Rc were 0.6 mM and 0.4 mM, while the Kcat/Km were 181.5 s-1 mM-1 and 197.8 s-1 mM-1, respectively. More than 90% of ginsenoside Rc could be transformed by 12 U/mL purified BsAbfA at 40 °C and pH 5 in 24 h. The results of molecular docking and site-directed mutagenesis suggested that the E173 and E292 variants for BsAbfA are important in recognizing ginsenoside Rc effectively, and to make it enter the active pocket to hydrolyze the outer arabinofuranosyl moieties at C20 position. These remarkable properties and the catalytic mechanism of BsAbfA provide a good alternative for the effective biotransformation of the major ginsenoside Rc into Rd.


Asunto(s)
Sustitución de Aminoácidos , Bacillus subtilis , Proteínas Bacterianas , Ginsenósidos/química , Glicósido Hidrolasas , Mutagénesis Sitio-Dirigida , Bacillus subtilis/enzimología , Bacillus subtilis/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Glicósido Hidrolasas/química , Glicósido Hidrolasas/genética , Mutación Missense , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética
5.
J Med Chem ; 64(7): 4071-4088, 2021 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-33761253

RESUMEN

Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design of novel isoindolinone-based MDM2 inhibitors. MDM2 X-ray crystallography, quantum mechanics ligand-based design, and metabolite identification all contributed toward the discovery of potent in vitro and in vivo inhibitors of the MDM2-p53 interaction with representative compounds inducing cytostasis in an SJSA-1 osteosarcoma xenograft model following once-daily oral administration.


Asunto(s)
Antineoplásicos/farmacología , Isoindoles/farmacología , Osteosarcoma/tratamiento farmacológico , Multimerización de Proteína/efectos de los fármacos , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Estabilidad de Medicamentos , Femenino , Humanos , Isoindoles/síntesis química , Isoindoles/metabolismo , Macaca fascicularis , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Microsomas Hepáticos/metabolismo , Estructura Molecular , Unión Proteica , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto
6.
Molecules ; 25(24)2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33322563

RESUMEN

The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of N1-substituted pyrimidine-2,4,6(1H,3H,5H)-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones ('pyranopyrimidinones'), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)propanamides) with a diversity of substituents. Cleavage of the pyranopyrimidinones with an aniline was facilitated in 2,2,2-trifluoroethanol under microwave irradiation. Compounds were tested against Escherichia coli, Staphylococcus aureus, the yeast Schizosaccharomyces pombe, and the pathogenic fungus Candida albicans. No compounds exhibited activity against E. coli, whilst one compound was weakly active against S. aureus. Three compounds were strongly active against S. pombe, but none was active against C. albicans.


Asunto(s)
Alquenos/química , Antibacterianos/farmacología , Antifúngicos/farmacología , Bioensayo/métodos , Pruebas de Sensibilidad Microbiana , Barbitúricos/síntesis química , Candida albicans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Concentración 50 Inhibidora , Conformación Molecular , Piranos , Schizosaccharomyces/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Trifluoroetanol/química
7.
PLoS One ; 15(3): e0229341, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32150552

RESUMEN

Very poor reclaimed soil quality and weak microbial activity occur in the reclamation area of a coal gangue landfill in the Loess Hills. The fourth and fifth years after farmland soil was reclaimed were studied, and the changes in and carbon source utilization characteristics of rhizosphere (R) and non-rhizosphere (S) soil microorganisms under organic and inorganic (OF), inorganic (F), and organic (O) fertilizer application and a control treatment (CK) in soybean (S) and maize (M) rotation systems were compared and analysed in Guljiao Tunlan, Shanxi Province, China. Biolog-EcoPlate technology was used to analyse the mechanism of soil characteristic change from the perspective of soil microbial metabolism function to provide a theoretical basis for reclamation and ecological reconstruction in this area. The average well colour development (AWCD) absorption and Shannon-Wiener index values of soybean and maize rhizosphere microorganisms were higher than those of non-rhizosphere microorganisms, and the mean value of the fertilizer treatment was higher than that for CK. Principal component analysis shows the main carbon sources that impact the functional diversity of the soybean rhizosphere and non-rhizosphere soil communities are a-cyclodextrin, a-D-lactose, ß-methyl D-glucoside, and glucose-1-phosphate and L-phenylalanine, while those for the maize rhizosphere and non-rhizosphere soil communities are D-cellobiose, glucose-1-phosphate, ß-methyl D-glucoside, methyl pyruvate, D-galactosate gamma lactone, D-mannitol, N-acetyl-D-glucosamine, D-galactosalonic acid, and L-serine. The comprehensive utilization score of the non-rhizosphere soil carbon source in the maize season increased with respect to that in the soybean season, and the maximum increase was 1.09 under the OF treatment. Redundancy analysis showed that the soil nutrient factors driving the changes in the metabolic function diversity index values of the rhizosphere and non-rhizosphere soil microbial communities in the different crop seasons in the reclamation area differed, but they were all related to the soil organic matter and available phosphorus. This may explain why OF treatment is the most beneficial to soil fertility under the rotation system in mining reclamation areas.


Asunto(s)
Bacterias/metabolismo , Biodiversidad , Producción de Cultivos/métodos , Fertilizantes , Rizosfera , Microbiología del Suelo , Zea mays/crecimiento & desarrollo , Bacterias/clasificación , Carbón Mineral , Microbiota , Instalaciones de Eliminación de Residuos , Zea mays/efectos de los fármacos , Zea mays/metabolismo , Zea mays/microbiología
8.
J Microbiol Biotechnol ; 29(3): 410-418, 2019 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-30518022

RESUMEN

To investigate a novel ß-glucosidase from Bifidobacterium breve ATCC 15700 (BbBgl) to produce compound K (CK) via ginsenoside F2 by highly selective and efficient hydrolysis of the C-3 glycoside from ginsenoside Rd, the BbBgl gene was cloned and expressed in E. coli BL21. The recombinant BbBgl was purified by Ni-NTA magnetic beads to obtain an enzyme with specific activity of 37 U/mg protein using pNP-Glc as substrate. The enzyme activity was optimized at pH 5.0, 35°C, 2 or 6 U/ml, and its activity was enhanced by Mn2+ significantly. Under the optimal conditions, the half-life of the BbBgl is 180 h, much longer than the characterized ß-glycosidases, and the Km and Vmax values are 2.7 mM and 39.8 µmol/mg/min for ginsenoside Rd. Moreover, the enzyme exhibits strong tolerance against high substrate concentration (up to 40 g/l ginsenoside Rd) with a molar biotransformation rate of 96% within 12 h. The good enzymatic properties and gram-scale conversion capacity of BbBgl provide an attractive method for large-scale production of rare ginsenoside CK using a single enzyme or a combination of enzymes.


Asunto(s)
Bifidobacterium breve/metabolismo , Ginsenósidos/metabolismo , Glucosa/metabolismo , Monosacáridos/metabolismo , beta-Glucosidasa/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Bifidobacterium breve/genética , Biotransformación , Clonación Molecular , Pruebas de Enzimas , Estabilidad de Enzimas , Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Ginsenósidos/biosíntesis , Ginsenósidos/química , Glicósidos , Concentración de Iones de Hidrógeno , Hidrólisis , Cinética , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , beta-Glucosidasa/genética , beta-Glucosidasa/aislamiento & purificación
9.
J Liposome Res ; 29(4): 322-331, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29745740

RESUMEN

Background and objective: The combination of two or more different mechanisms of drugs in the treatment of cancer has become one of the effective methods. The purpose of this study was to successfully prepare a non-viral delivery system that could efficiently co-delivery siRNA and gambogenic acid (GNA) to improve the anti-cancer efficiency in HepG2 cells. Methods: The delivery system was prepared by a two-step method. First, the GNA-anionic liposome took shape by a solvent evaporation method, and then the liposome was bound to the PEI/siRNA complex by electrostatic interaction to form the final carrier system (lipopolyplexes). Agarose gel electrophoresis, MTT, particle size and zeta potential were detected to analyse the lipopolyplexes formation. The transfection efficiency of siRNA was determined by confocal laser scanning microscopy and flow cytometry. Western blotting was used to assess the VEGF protein expression levels of HepG2 cells. The cell apoptosis assay was used to assess the anti-tumour superiority of lipopolyplexes. Results: GNA-PEI/siRNA-liposome (lipopolyplexes) are significantly less cytotoxicity compared to PEI mediated carriers. Simultaneously, the results of flow cytometry and confocal laser scanning microscopy indicated that the lipopolyplexes could successfully carry siRNA into the cytoplasm, and the western-blot result evidence that the delivery system has a potential for VEGF to express down. Also compared with the control group, the results of apoptosis test suggest that the lipopolyplexes can significantly promote cell apoptosis. Conclusion: The delivery system has a potential in the combination of various drugs for cancer therapy in future.


Asunto(s)
Antineoplásicos/química , Liposomas/química , Polietileneimina/química , ARN Interferente Pequeño/química , Factor A de Crecimiento Endotelial Vascular/genética , Xantenos/química , Aniones/química , Apoptosis/efectos de los fármacos , Permeabilidad de la Membrana Celular , Supervivencia Celular/efectos de los fármacos , Terapia Combinada/métodos , Citoplasma/metabolismo , Liberación de Fármacos , Silenciador del Gen/efectos de los fármacos , Terapia Genética/métodos , Células Hep G2 , Humanos
10.
Ying Yong Sheng Tai Xue Bao ; 28(1): 281-290, 2017 Jan.
Artículo en Chino | MEDLINE | ID: mdl-29749213

RESUMEN

A thermocline characteristics contour on a spatial overlay map was plotted using data collected on a monthly basis from Argo buoys and data of monthly CPUE (catch per unit effort) bigeye tuna (Thunnus obesus) long-lines fishery from the Western and Central Pacific Fisheries Commission (WCPFC) to evaluate the relationship between fishing grounds temporal-spatial distribution of bigeye tuna and thermocline characteristics in the Western and Central Pacific Ocean (WCPO). In addition, Numerical methods were used to calculate the optimum ranges of thermocline characteristics of the central fishing grounds. The results showed that the central fishing grounds were mainly distributed between 10° N and 10° S. Seasonal fishing grounds in the south of equator were related to the seasonal variations in the upper boundary temperature, depth and thickness of thermocline. The fishing grounds were observed in areas where the upper boundary depth of thermocline was deep (70-100 m) and the thermocline thickness was more than 60 m. The CPUE tended to be low in area where the thermocline thickness was less than 40 m. The optimum upper boundary temperature range for distribution was 26-29 ℃, and the CPUE was mostly lower than the threshold value (Q3) of central fishing grounds when the temperature was higher than 29 ℃ or lower than 26 ℃. The temporal and spatial distribution of the fishing grounds was influenced by the seasonal variations in upper boundary depth and thermocline thickness. The central fishing grounds in the south of equator disappeared when the upper boundary depth of thermocline decreased and thermocline thickness became thinner. The lower boundary temperature and depth of thermocline and thermocline strength has little variation, but were strongly linked to the location of fishing grounds. The fishing grounds were mainly located between the two high-value zones of the lower boundary depth of thermocline, where the temperature was lower than 13 ℃ and the strength was high. When the depth was more than 300 m or less than 150 m, the lower boundary temperature was more than 17 ℃, or the strength was low, the CPUE tended to be low. The optimum range of thermocline characteristics was calculated using frequency analysis and empirical cumulative distribution function. The results showed that the optimum ranges for upper boundary thermocline temperature and depth were 26-29 ℃ and 70-110 m, the optimum lower boundary thermocline temperature and depth ranges were 11-13 ℃ and 200-280 m, the optimum ranges for thermocline thickness and thermocline strength were 50-90 m and 0.1-0.16 ℃·m-1, respectively. The paper documented the distribution interval of thermocline characteristics for central fishing ground of the bigeye tuna in WCPO. The results provided a reference for improving the efficiency of pelagic bigeye tuna fishing operation and tuna resource management in WCPO.


Asunto(s)
Explotaciones Pesqueras , Atún , Distribución Animal , Animales , Océano Pacífico , Estaciones del Año , Temperatura
11.
Bioorg Med Chem Lett ; 26(11): 2680-4, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27106712

RESUMEN

Rutin exists in medicinal herbs, fruits, vegetables, and a number of plant-derived sources. Dietary sources containing rutin are considered beneficial because of their potential protective roles in multiple diseases related to oxidative stresses. In the present study, the change and antioxidation activity of rutin in Maillard reaction with lysine through a heating process were investigated. There is release of glucose and rhamnose that interact with lysine to give Maillard reaction products (MRPs), while rutin is converted to less-polar quercetin and a small quantity of isoquercitrin. Because of their high cell-membrane permeability, the rutin-lysine MRPs increase the free radical-scavenging activity in HepG2 cells, showing cellular antioxidant activity against Cu(2+)-induced oxidative stress higher than that of rutin. Furthermore, the MRPs significantly increased the Cu/Zn SOD (superoxide dismutase) activity and Cu/Zn SOD gene expression of HepG2 cells, consequently enhancing antioxidation activity.


Asunto(s)
Antioxidantes/farmacología , Lisina/farmacología , Rutina/farmacología , Antioxidantes/química , Permeabilidad de la Membrana Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Lisina/química , Reacción de Maillard , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Rutina/química , Relación Estructura-Actividad , Superóxido Dismutasa/metabolismo
12.
Dalton Trans ; 45(12): 5339-55, 2016 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-26905013

RESUMEN

Reactions between 4'-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m- or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)2](p-SO3C6H4CH3) (1), [Cu(OCOPh)2L] (2), [Cu(o-OCOC6H4OH)2L] (3), [Cu(m-OCOC6H4OH)2L]4·MeOH (·MeOH) and [Cu(p-OCOC6H4OH)2L]5·2H2O (·2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2-5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular π···π stacking interactions could also be found in 2-5 (in the 3.569-3.651 Å range and involving solely the pyridyl rings). Medium-strong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H2O2. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage.

13.
Pharmazie ; 70(8): 511-4, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26380519

RESUMEN

Five indolin-2-one derivatives bearing piperazinylbutyl side chains attached to the amide nitrogen were synthesized from 2-indolinone. 1-(4-Bromobutyl)-indolin-2-one was reacted with 1-piperazinecarboxaldehyde to form 1-(4-(4-formyl-1-piperazinyl)butyl)indolin-2-one (2). In the presence of H2SO4, the aldehyde moiety was removed from 1-(4-(4-formyl-1-piperazinyl)butyl)indolin-2-one and then 1-(4-(1-piperazinyl)butyl)indolin-2-one (3) was obtained, this compound was reacted with benzaldehyde derivatives to give the target compounds 4 a-e by N-alkylation reaction. The structures of the intermediates and the target compounds were characterized by 1H NMR, ESI-MS spectra and elemental analyses. In vitro receptor binding assays at D2, D3, D4 receptor subtypes of the target compounds were performed and the five compounds showed selectivity towards D2-like receptors. Among them, 1-(4-(4-(4-hydroxybenzy)-1-piperazinyl)butyl) indolin-2-one (4c) exhibited a remarkable affinity and selectivity to D4 receptor with K(i) value of 0.5 nM. The results indicated that 1-(4-(4-(4-hydroxybenzy)-1-piperazinyl)butyl)indolin-2-one might be a potential dopamine D4 receptor ligand.


Asunto(s)
Indoles/síntesis química , Indoles/farmacología , Receptores de Dopamina D4/efectos de los fármacos , Animales , Células CHO , Cricetinae , Cricetulus , Indicadores y Reactivos , Indoles/metabolismo , Ligandos , Espectroscopía de Resonancia Magnética , Receptores de Dopamina D4/metabolismo , Espectrometría de Masa por Ionización de Electrospray , Relación Estructura-Actividad
14.
Biotechnol Lett ; 37(10): 2091-6, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26087948

RESUMEN

OBJECTIVES: To improve the production of ginsenoside Rg1 in Panax ginseng. RESULTS: The α-L-rhamnosidase gene from Bifidobacterium breve (BbRha) was overexpressed into hairy root culture system using Agrobacterium rhizogenes A4. Ginsenoside Rg1 in hairy roots was obtained following transformation via overexpressed gene representing 2.2-fold higher than those of control lines. Several overexpression transgenic hairy root lines were obtained exhibiting markedly increased levels of the corresponding α-L-rhamnosidase enzymatic activity relative to control. Ginsenoside Rg1 levels in the transgenic lines were higher (2.2-fold) than those of control after following 30 days culturing, while ginsenoside Re contents in tested transgenic lines were found to be lower. The transgenic hairy roots harboring α-L-rhamnosidase gene improved the accumulation of ginsenoside Rg1 up to 3.6 mg g(-1) dry weight. CONCLUSION: BbRha gene selectively enhances the production of ginsenoside Rg1 in P. ginseng hairy roots.


Asunto(s)
Bifidobacterium/enzimología , Ginsenósidos/metabolismo , Glicósido Hidrolasas/biosíntesis , Ingeniería Metabólica , Panax/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Agrobacterium/genética , Bifidobacterium/genética , Expresión Génica , Glicósido Hidrolasas/genética , Raíces de Plantas/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Transformación Genética
15.
Future Med Chem ; 7(5): 631-45, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25921402

RESUMEN

Potent and selective small-molecule inhibitors of the p53-MDM2 interaction intended for the treatment of p53 wild-type tumors have been designed and optimized in a number of chemical series. This review details recent disclosures of compounds in advanced optimization and features key series that have given rise to clinical trial candidates. The structure-activity relationships for inhibitor classes are discussed with reference to x-ray structures, and common structural features are identified.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Mapas de Interacción de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Cristalografía por Rayos X , Humanos , Imidazoles/química , Imidazoles/farmacología , Imidazoles/uso terapéutico , Indoles/química , Indoles/farmacología , Indoles/uso terapéutico , Modelos Moleculares , Neoplasias/metabolismo , Oxindoles , Piperazinas/química , Piperazinas/farmacología , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-mdm2/química , Pirrolidinas/química , Pirrolidinas/farmacología , Pirrolidinas/uso terapéutico , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Relación Estructura-Actividad , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/química , para-Aminobenzoatos/química , para-Aminobenzoatos/farmacología , para-Aminobenzoatos/uso terapéutico
16.
Biotechnol Lett ; 37(6): 1257-64, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25724715

RESUMEN

OBJECTIVES: To biotransform rutin into isoquercitrin. RESULTS: A α-L-rhamnosidase from Bifidobacterium breve was produced by using Escherichia coli BL21 for biotransformation of rutin to isoquercitrin. The enzyme was purified by Ni(2+)-NTA chromatography to yield a soluble protein with a specific activity of 56 U protein mg(-1). The maximum enzyme activities were at pH 6.5, 55 °C, 20 mM rutin, and 1.2 U enzyme ml(-1). Under optimal conditions, the half-life of the enzyme was 96 h. The K m and V max values were 2.2 mM, 56.4 µmol mg(-1) min(-1) and 2.1 mM, 57.5 µmol mg(-1) min(-1) using pNP-Rha and rutin as substrates, respectively. The kinetic behavior indicated that the recombinant α-L-rhamnosidase has good catalytic performance for producing isoquercitrin. 20 mM rutin was biotransformed into 18.25 and 19.87 mM isoquercitrin after 60 and 240 min. CONCLUSION: The specific biotransformation of rutin to isoquercitrin using recombinant α-L-rhamnosidase from B. breve is a feasible method for use in industrial processes.


Asunto(s)
Bifidobacterium/enzimología , Escherichia coli/metabolismo , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Quercetina/análogos & derivados , Rutina/metabolismo , Bifidobacterium/genética , Biotransformación , Cromatografía de Afinidad , Escherichia coli/enzimología , Escherichia coli/genética , Glicósido Hidrolasas/aislamiento & purificación , Concentración de Iones de Hidrógeno , Cinética , Quercetina/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Temperatura
17.
Org Lett ; 14(16): 4198-201, 2012 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-22870948

RESUMEN

A new rhodamine spiro scaffold with a six-membered reactive ring was developed by inserting a nitrogen atom in the known probe rhodamine B spiro thiohydrazide, which switched the recognition preference of the probe from Hg(2+) to Cu(2+). This probe is shown to be an efficient "turn-on" fluorescent chemodosimeter for Cu(2+) in a neutral aqueous medium. Mechanism studies suggested that the probe opened its spiro-ring by a Cu(2+)-induced transformation of the cyclic thiosemicarbazide moiety to an isothiocyanate group.


Asunto(s)
Cobre/análisis , Colorantes Fluorescentes/síntesis química , Hidrazinas/síntesis química , Mercurio/análisis , Rodaminas/síntesis química , Compuestos de Espiro/química , Colorantes Fluorescentes/química , Hidrazinas/química , Estructura Molecular , Rodaminas/química , Agua
18.
J Chromatogr A ; 1218(37): 6498-504, 2011 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-21803361

RESUMEN

One monomer molecularly imprinted polymer coatings were first synthesized in fused silica capillary columns with 2-methacrylamidopropyl methacrylate (MAM) as single functional monomer in addition to a cross-linking monomer. Since MAM may generate no or little EOF, a strategy of precursor of polymerization, which does not interfere with the formation of defined imprints, was used to introduce an ionizable functional monomer to generate a stable electroosmotic flow for electrochromatography (CEC) by post-polymerization hydrolization. The resulting MAM-based open-tubular imprinted capillary was able to separate enantiomers by means of CEC. The resolution of enantiomers separation achieved on S-amlodipine-imprinted capillary was up to 16.1. The strong recognition ability (selectivity factor was 3.23) and high column performance (theory plates was 26,053 plates m(-1)) of template were obtained. The MIP coatings were also prepared using either S-naproxen or S-ketoprofen as template molecule. The resolutions of enantiomers separation were 2.20 and 4.56, respectively. The results illustrate that the synthesis of MIP using one monomer is not only an experimental-simplified process, but also an approach to producing chiral stationary phase with high efficiency and selectivity.


Asunto(s)
Electrocromatografía Capilar/métodos , Impresión Molecular , Polímeros/química , Amlodipino/química , Amlodipino/aislamiento & purificación , Electrocromatografía Capilar/instrumentación , Concentración de Iones de Hidrógeno , Cetoprofeno/química , Cetoprofeno/aislamiento & purificación , Microscopía Electrónica de Rastreo , Naproxeno/química , Naproxeno/aislamiento & purificación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estereoisomerismo
19.
Zhongguo Zhen Jiu ; 31(7): 613-6, 2011 Jul.
Artículo en Chino | MEDLINE | ID: mdl-21823284

RESUMEN

OBJECTIVE: To compare the differences in the therapeutic effect on diabetic peripheral neuropathy between the combined therapy of electroacupuncture and acupoint injection and the simple acupoint injection. METHODS: Under the satisfactory control of blood glucose, 60 cases of diabetic peripheral neuropathy were divided randomly into two groups, 30 cases in each one. In electroacupuncture plus acupoint injection group (group A), electroacupuncture and acupoint injection with Methylcobalamin were administered. Penetrating acupuncture was applied from Gongsun (SP 4) to Quanzhong (Extra) and from Yongquan (KI 1) to Taichong (LR 3) mainly. Acupoint injection was administered on Sanyinjiao (SP 6). In acupoint injection group (group B), only acupoint injection with Methylcobalamin was provided on Sanyinjiao (SP 6). After 2 sessions of treatment, the conduction velocity of ulnar nerve and tibial nerve was measured. The scores of Chinese medicine syndrome and diabetic peripheral neuropathy were recorded before and after treatment in two groups. RESULTS: The effective rates were 90.0% (27/30) and 63.3% (19/30) in group A and group B respectively, presenting significant statistical difference (P < 0.05). After treatment, the motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) of ulnar nerve and tibial nerve in group A were higher than those in group B (P < 0.05, P < 0.01). After treatment, the score of Chinese medicine syndrome in group A was lower than that in group B (14.36 +/- 1.88 vs 26.58 +/- 3.52, P < 0.01), the score of diabetic peripheral neuropathy in group A was lower than that in group B (12.86 +/- 4.28 vs 17.89 +/- 4.35, P < 0.01). CONCLUSION: Electroacupuncture and acupoint injection with Methylcobalamin achieve a significant clinical efficacy on diabetic neuropathy and its efficacy is superior to that of simple acupoint injection with Methylcobalamin. This therapy can effectively increase nerve conduction velocity, control and relieve the symptoms of diabetic peripheral neuropathy.


Asunto(s)
Puntos de Acupuntura , Neuropatías Diabéticas/terapia , Electroacupuntura , Vitamina B 12/análogos & derivados , Adulto , Anciano , Terapia Combinada , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/fisiopatología , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Nervio Tibial/fisiopatología , Vitamina B 12/administración & dosificación
20.
Chin Med J (Engl) ; 123(20): 2807-11, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21034587

RESUMEN

BACKGROUND: Smoking is known to be a strong risk factor for premature atherosclerosis, acute myocardial infarction (AMI) and sudden cardiac death. According to a cross-sectional survey conducted in 2000 - 2001 in China, the prevalence of smoking among the Chinese men was 60.2%, the highest prevalence in the world. Up to date, the relationship between smoking and AMI in Chinese male smokers is still unclear. This study analyzed the baseline characteristics for male smokers hospitalized with AMI and investigated the effect of cigarette smoking on their clinical outcomes. METHODS: A total of 890 men aged 18 years or over with AMI were prospectively recruited from 1 January 2007 to 31 December 2009 from Shanxi Provincial People's Hospital. Patients were grouped into smokers and nonsmokers. The relationships between baseline characteristics and clinical outcomes were tested using either the chi-square test for trend for discrete variables or analysis of variance for continuous variables. RESULTS: Smokers accounted for 66.7% (594), more than twice of nonsmokers (296 (33.3%)), and were averaged 7 years younger ((56.61 ± 11.44) vs. (63.61 ± 11.62) years, P < 0.001). Smokers had the higher rate of TIMI flow grade 2 or 3 after thrombolytic therapy (42.4% vs. 24.5%, P = 0.002), 1 vessel disease (25.5% vs. 14.5%, P = 0.003) than nonsmokers. Smokers had better in-hospital outcome with lower in-hospital mortality rate than nonsmokers (6.2% vs. 10.8%, P = 0.023). CONCLUSIONS: Male smokers suffered from AMI in this study presented an average of 7 years earlier than nonsmokers and were more than twice as likely to have AMI as nonsmokers in China. Smoking appeared to result in earlier infarction, especially ST elevated myocardial infarction in otherwise healthier patients who are likely to survive.


Asunto(s)
Infarto del Miocardio/mortalidad , Fumar/efectos adversos , Enfermedad Aguda , Adulto , Anciano , China , Mortalidad Hospitalaria , Hospitalización , Humanos , Masculino , Persona de Mediana Edad
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