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1.
Ecotoxicol Environ Saf ; 248: 114329, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36442400

RESUMEN

The public health harms caused by fine particulate matter (PM2.5) have become a global focus, with PM2.5 exposure recognized as a critical risk factor for global morbidity and mortality. Chronic inflammation is the common pathophysiological feature of respiratory diseases induced by PM2.5 and is the most critical cause of all these diseases. However, presently there is a lack of effective preventive and therapeutic approaches for inflammatory lung injuries caused by PM2.5 exposure. Baicalin is a herb-derived effective flavonoid compound with multiple health benefits. This study established a murine lung inflammatory injury model via inhalation of PM2.5 aerosols. The data showed that after baicalin intervention, lung injury pathological score of baicalin (4.16 ± 0.54, 3.33 ± 0.76, 4.00 ± 0.45) and claricid (3.00 ± 0.78) treatments were markedly lower than PM2.5-treated mice (6.17 ± 0.31), and pathological damage was alleviated. Compared to the PM2.5 group, the spleen and lung indexes in the baicalin and claricid groups were significantly reduced. The inflammatory cytokines of TNF-α, IL-18, and IL-1ß in serum, alveolar lavage fluid, and lung tissue were significantly decreased in the baicalin and claricid groups. The expressions of inflammatory pathway-related genes and proteins HMGB1, NLRP3, ASC, and caspase-1 were up-regulated in the PM2.5 group. The expressions of these genes and proteins were significantly decreased following baicalin treatment. The lung function indicators showed that the MV (65.94 ± 8.19 mL), sRaw (1.79 ± 0.08 cm H2O.s), and FRC (0.52 ± 0.01 mL) in the PM2.5 group were higher than in the control and baicalin groups, and respiratory function was improved by baicalin. PM2.5 exposure markedly altered the bacterial composition at the genus level. The dominant flora relative abundances of uncultured_bacterium_f_Muribaculaceae, Streptococcus, and Lactobacillus, were decreased from the control group (9.20%, 8.53%, 6.21%) to PM2.5 group (6.26%, 5.49%, 4.77%), respectively. Following baicalin intervention, the relative abundances were 9.72%, 6.65%, and 3.57%, respectively. Therefore, baicalin could potentially prevent and improve mice lung inflammatory injury induced by PM2.5 exposure. Baicalin might provide a protective role by balancing oropharyngeal microbiota and affecting the expression of the HMGB1/Caspase1 pathway.


Asunto(s)
Proteína HMGB1 , Lesión Pulmonar , Ratones , Animales , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , Ratones Endogámicos , Flavonoides/farmacología , Flavonoides/uso terapéutico , Pulmón
2.
Antonie Van Leeuwenhoek ; 114(2): 113-127, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33387140

RESUMEN

Using the culturomics approach, we isolated a new Streptococcus species, strain C17T, from the oropharynx mucosa sample of a healthy 5-year-old child living in Shenyang, China. We studied the phenotypic, phylogenetic, and genomic characteristics of strain C17T, which was identified as a Gram-positive, coccus-shaped, non-motile, aerobic, catalase-negative bacteria. Its growth temperatures ranged from 20 to 42 °C, with optimal growth at 37 °C. Acid production could be inhibited by two sugars, trehalose and raffinose. In C17T, the reactions for enzyme lipase (C14) were confirmed to be negative, whereas those for alkaline phosphatase, α-glucosidase, and hippuric acid hydrolysis were positive. The C17T genome contained 2,189,419 base pairs (bp), with an average G+C content of 39.95%, encoding 2092 genes in total. The 16S ribosomal RNA sequence showed 99.8% similarity with the newly identified Streptococcus pseudopneumoniae ATCC BAA-960T. The main fatty acid components in C17T were C16:0, C18:1 w7c, C18:0, and C18:1 w9c, all of which can be found in other species of the Streptococcus genus. Strain C17T showed high susceptibility to clindamycin, linezolid, vancomycin, chloramphenicol, and cefepime, and moderate susceptibility to erythromycin. The obtained dDDH value between strain C17T and the closest species was 52.9%. In addition, the whole genome sequence of strain C17T had an 82.21-93.40% average nucleotide identity (ANI) with those strains of closely related Streptococcus species, indicating that the strain C17T was unique among all Streptococcus species. Based on these characteristics, we determine that C17T is a novel species, named Streptococcus symci sp. nov. (= GDMCC 1.1633 = JCM 33582).


Asunto(s)
Fosfolípidos , Streptococcus , Técnicas de Tipificación Bacteriana , Preescolar , ADN Bacteriano/genética , Ácidos Grasos , Genómica , Humanos , Hibridación de Ácido Nucleico , Orofaringe , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Streptococcus/genética
3.
Curr Microbiol ; 78(7): 2821-2827, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34031726

RESUMEN

A Gram-positive, catalase-negative, coccus-shaped, chain-forming organism isolated from the oropharynx of a healthy child in Shenyang, China, was subjected to phenotypic and molecular taxonomic analyses. 16S rRNA sequence analysis indicated that this bacterium represents a new member of the genus Streptococcus and is closely related to Streptococcus oralis subsp. dentisani DSM 27088. According to DNA-DNA hybridization analysis, strain D19T was less than 70% similar to other strains with close genetic relationships. Fatty acid analysis, physiological, and biochemical tests showed that strain D19T was different from the published Streptococcus species. The genome of strain D19T is 2,023,003 bp long with a GC content of 39.9 mol%. It contains 1889 protein-coding genes and 50 RNA genes. These results show that Streptococcus shenyangsis sp. nov. strain D19T is a new species.


Asunto(s)
Orofaringe , Streptococcus , Técnicas de Tipificación Bacteriana , Niño , China , ADN Bacteriano/genética , Humanos , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Streptococcus/genética
4.
Bioorg Chem ; 101: 103965, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32485471

RESUMEN

New Delhi Metallo-ß-lactamase-1 (NDM-1), a Zn (II)-dependent enzyme, can catalyze the hydrolysis of almost all ß-lactam antibiotics including carbapenems, resulting in bacterial antibiotic resistance, which threatens public health globally. Based on our finding that H2dedpa is as an efficient NDM-1 inhibitor, a series of H2dedpa derivatives was systematically prepared. These compounds exhibited significant activity against NDM-1, with IC50 values 0.06-0.94 µM. In vitro, compounds 6k and 6n could restore the activity of meropenem against Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis possessing either NDM or IMP. In particular, the activity of meropenem against E. coli producing NDM-4 could be improved up to 5333 times when these two compounds were used. Time-kill cell-based assays showed that 99.9% of P. mirabilis were killed when treated with meropenem in combination with compound 6k or 6n. Furthermore, compounds 6k and 6n were nonhemolytic (HC50 > 1280 µg/mL) and showed low toxicity toward mammalian (HeLa) cells. Mechanistic studies indicated that compounds 6k and 6n inhibit NDM-1 by chelating the Zn2+ ion of the enzyme.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Etilaminas/farmacología , Piridinas/farmacología , beta-Lactamasas/efectos de los fármacos , Antibacterianos/farmacología , Etilaminas/química , Células HeLa , Hemólisis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Piridinas/química
5.
J Nat Prod ; 82(5): 1391-1395, 2019 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-31013089

RESUMEN

Raistrickindole A (1), a new indole diketopiperazine alkaloid containing an unusual pyrazino[1',2':2,3][1,2]oxazino[6,5- b]indole tetraheterocyclic ring system, a new benzodiazepine derivative, raistrickin (2), and the known haenamindole (3) and sclerotigenin (4) were isolated from the marine-derived fungus Penicillium raistrickii IMB17-034. Their structures were elucidated by extensive spectroscopic analyses and TDDFT calculations of the NMR and ECD data. Compounds 1 and 2 showed inhibitory activities against the hepatitis C virus.


Asunto(s)
Antivirales/química , Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Penicillium/química , Antibióticos Antineoplásicos/farmacología , Línea Celular , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Fermentación , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular
6.
Molecules ; 24(15)2019 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-31382398

RESUMEN

A new pyrazine derivative, trypilepyrazinol (1), a new α-pyrone polyketide, (+)-neocitreoviridin (2), and a new ergostane analogue, 3ß-hydroxyergosta-8,14,24(28)-trien-7-one (3), were isolated and characterized along with five known compounds from the marine-derived fungus Penicillium sp. IMB17-046. The structures of these new compounds were determined using spectroscopic data analyses (HRESIMS, 1D- and 2D-NMR), X-ray crystallography analysis, and TDDFT ECD calculation. Compounds 1 and 3 exhibited broad-spectrum antiviral activities against different types of viruses, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza A virus (IAV), with IC50 values ranging from 0.5 to 7.7 µM. Compounds 1 and 2 showed antibacterial activities against Helicobacter pylori, a causative pathogen of various gastric diseases, with minimum inhibitory concentration (MIC) values of 1-16 µg/mL.


Asunto(s)
Antivirales/farmacología , Organismos Acuáticos/química , Productos Biológicos/farmacología , Penicillium/química , Antivirales/química , Productos Biológicos/química , Línea Celular , VIH/efectos de los fármacos , Humanos , Virus de la Influenza A/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular
7.
Bioorg Med Chem Lett ; 28(2): 214-221, 2018 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-29248295

RESUMEN

The emergence of antibiotic drug (like carbapenem) resistance is being a global crisis. Among those resistance factors of the ß-lactam antibiotics, the metallo-ß-lactamases (MBLs) is one of the most important reasons. In this paper, a series of cyclic dithiocarbamate compounds were synthesized and their inhibition activities against MBLs were initially tested combined with meropenem (MEM) by in vitro antibacterial efficacy tests. Sodium 1,4,7-triazonane-1,4,7-tris(carboxylodithioate) (compound 5) was identified as the most active molecule to restore the activity of MEM. Further anti-bacterial effectiveness assessment, compound 5 restored the activity of MEM against Escherichia coli, Citrobacter freundii, Proteus mirabilis and Klebsiella pneumonia, which carried resistance genes of blaNDM-1. The compound 5 was non-hemolytic, even at a concentration of 1000 µg/mL. This compound was low toxic toward mammalian cells, which was confirmed by fluorescence microscopy image and the inhibition rate of HeLa cells. The Ki value of compounds 5 against NDM-1 MBL was 5.63 ±â€¯1.27 µM. Zinc ion sensitivity experiments showed that the inhibitory effect of compound 5 as a MBLs inhibitor was influenced by zinc ion. The results of the bactericidal kinetics displayed that compound 5 as an adjuvant assisted MEM to kill all bacteria. These data validated that this NOTA dithiocarbamate analogue is a good inhibitor of MBLs.


Asunto(s)
Antibacterianos/farmacología , Compuestos Heterocíclicos/farmacología , Inhibidores de beta-Lactamasas/farmacología , beta-Lactamasas/metabolismo , Antibacterianos/síntesis química , Antibacterianos/química , Supervivencia Celular/efectos de los fármacos , Citrobacter freundii/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Células HeLa , Compuestos Heterocíclicos/síntesis química , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos con 1 Anillo , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Proteus mirabilis/efectos de los fármacos , Relación Estructura-Actividad , Inhibidores de beta-Lactamasas/síntesis química , Inhibidores de beta-Lactamasas/química
8.
J Nat Prod ; 81(1): 178-187, 2018 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-29308897

RESUMEN

Analysis of the whole genome sequence of Streptomyces sp. IMB7-145 revealed the presence of seven type I polyketide synthase biosynthetic gene clusters, one of which was highly homologous to the biosynthetic gene cluster of azalomycin F. Detailed bioinformatic analysis of the modular organization of the PKS gene suggested that this gene is responsible for niphimycin biosynthesis. Guided by genomic analysis, a large-scale cultivation ultimately led to the discovery and characterization of four new niphimycin congeners, namely, niphimycins C-E (1-3) and 17-O-methylniphimycin (4). The configurations of most stereocenters of niphimycins have not been determined to date. In the present study, the relative configurations were elucidated by spectroscopic analysis, including J-based analysis and the CNMR database method. Further, the full absolute configurations of niphimycins were completely proposed for the first time based on biosynthetic gene cluster analysis of the ketoreductase and enoylreductase domains for hydroxy- and methyl-bearing stereocenters. Compounds 1, 3, 4, and niphimycin Iα (5) showed antimicrobial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (MIC: 8-64 µg/mL), as well as cytotoxicity against the human HeLa cancer cell line (IC50: 3.0-9.0 µM). In addition, compounds 1 and 5 displayed significant activity against several Mycobacterium tuberculosis clinical isolates (MIC: 4-32 µg/mL).


Asunto(s)
Organismos Acuáticos/química , Streptomyces/química , Streptomyces/genética , Antibacterianos/química , Antibacterianos/farmacología , Línea Celular Tumoral , Genómica/métodos , Guanidinas/química , Guanidinas/farmacología , Células HeLa , Células Hep G2 , Humanos , Células K562 , Células MCF-7 , Macrólidos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Familia de Multigenes/genética , Sintasas Poliquetidas/genética
9.
Mar Drugs ; 16(10)2018 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-30241346

RESUMEN

Six new tetracenomycin congeners, saccharothrixones E⁻I (1⁻5) and 13-de-O-methyltetracenomycin X (6), were isolated from the rare marine-derived actinomycete Saccharothrix sp. 10-10. Their structures were elucidated by spectroscopic analysis and time-dependent density functional theory (TDDFT)-electronic circular dichroism (ECD) calculations. Saccharothrixones G (3) and H (4) are the first examples of tetracenomycins featuring a novel ring-A-cleaved chromophore. Saccharothrixone I (5) was determined to be a seco-tetracenomycin derivative with ring-B cleavage. The new structural characteristics, highlighted by different oxidations at C-5 and cleavages in rings A and B, enrich the structural diversity of tetracenomycins and provide evidence for tetracenomycin biosynthesis. Analysis of the structure⁻activity relationship of these compounds confirmed the importance of the planarity of the naphthacenequinone chromophore and the methylation of the polar carboxy groups for tetracenomycin cytotoxicity.


Asunto(s)
Actinomycetales/química , Antineoplásicos/farmacología , Organismos Acuáticos/química , Naftacenos/farmacología , Policétidos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Dicroismo Circular , Teoría Funcional de la Densidad , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Naftacenos/química , Naftacenos/aislamiento & purificación , Policétidos/química , Quinonas/química , Relación Estructura-Actividad
10.
Wei Sheng Yan Jiu ; 45(4): 648-662, 2016 Jul.
Artículo en Zh | MEDLINE | ID: mdl-29903338

RESUMEN

OBJECTIVE: To investigate the effect of PM2. 5on the respiratory tract flora in the SHR / NCrl rats. METHODS: Through the simulation of real air pollution and mixed gas exposure, the establishment of acute exposure to air pollution in low, medium and high concentration of animal models, to detect the distribution of bacterial flora before and after the dust exposure in the throat and respiratory mucosa of SHR rats. Analysis on the trend of micro ecology of respiratory tract was studied dynamically. RESULTS: The detection rate of anaerobic bacteria in SHR rats was 71. 8% and 20. 7% respectively, compared with the previous exposure to dust was high than 0. 6%, there were significant differences( P <0. 05). In the detection rate of anaerobic bacteria, the Tetanus bacillus and Clostridium in the respiratory tract of the exposed to dust rats was not detected. After the dust exposure, two kinds of bacteria respectively in 28 and 5 SHR rats were detected. The detection rate ofVeillonella in anaerobic bacteria was 53. 1%, there were significant differences( P <0. 05). The number of pathogenic bacteria in the aerobic bacteria after the dust exposure was increased, the detection rate also increased. The results showed that in the body the number and species of bacteria after the exposure to dust were changed. CONCLUSION: PM_(2. 5) as the carrier of harmful substance, when with breathing enter the human respiratory tract, will cause the normal flora in the body 's respiratory tract disorder. The pathogen bacteria is easy to be colonized and the detection rate is increased, which affecting the body healthy.


Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Monitoreo del Ambiente/métodos , Exposición por Inhalación/efectos adversos , Enfermedades Respiratorias/inducido químicamente , Contaminantes Atmosféricos/química , Contaminación del Aire/análisis , Animales , Polvo , Humanos , Exposición por Inhalación/análisis , Ratas , Ratas Endogámicas SHR , Enfermedades Respiratorias/etiología
11.
J Nat Prod ; 78(9): 2260-5, 2015 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-26317881

RESUMEN

Saccharothrixones A-C (1-3), three new aromatic polyketide seco-tetracenomycins, and saccharothrixone D (4), a new tetracenomycin analogue possessing opposite configurations at all of the stereogenic centers, were isolated from the marine-derived actinomycete Saccharothrix sp. 10-10. Compounds 1-3 represent the first examples of seco-tetracenomycins where the quinone ring B is cleaved and re-formed into a furanone ring. Their structures were elucidated by spectroscopic analyses and ECD calculations. The absolute configuration of 4 was confirmed by single-crystal X-ray diffraction analysis. Saccharothrixone D (4) showed in vitro cytotoxic activity against the HepG2 cancer cell line with an IC50 value of 7.5 µM.


Asunto(s)
Actinomycetales/química , Policétidos/aislamiento & purificación , Humanos , Estructura Molecular , Naftacenos , Policétidos/química
12.
Proc Natl Acad Sci U S A ; 109(43): 17412-7, 2012 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-23045703

RESUMEN

Mycobacterium tuberculosis kills about 2 million people annually and antibiotic resistance is a cause of increased mortality. Therefore, development of new antituberculosis drugs is urgent for the control of widespread tuberculosis infections. For this purpose, we performed an innovative screen to identify new agents that disrupt the function of ribosomes in M. tuberculosis. Two bacterial ribosomal proteins L12 and L10 interact with each other and constitute the stalk of the 50S ribosomal subunit, which recruits initiation and elongation factors (EFs) during translation. Therefore, the L12-L10 interaction should be essential for ribosomal function and protein synthesis. We established a yeast two-hybrid system to identify small molecules that block the interaction between L12 and L10 proteins from M. tuberculosis. Using this system, we identified two compounds T766 and T054 that show strong bactericidal activity against tuberculosis but with low toxicity to mice and other bacterial strains. Moreover, using surface plasmon resonance (SPR) assay, we have demonstrated that these compounds bind specifically to L12 to disrupt L12-L10 interaction. Overproduction of L12 protein, but not L10, lowers the antibacterial activity of T766 and T054, indicating that the ribosome is likely the cellular target. Therefore, our data demonstrate that this yeast two-hybrid system is a useful tool to identify unique antituberculosis agents targeting the ribosomal protein L12-L10 interaction.


Asunto(s)
Antituberculosos/farmacología , Proteínas Ribosómicas/metabolismo , Saccharomyces cerevisiae/genética , Antituberculosos/metabolismo , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Resonancia por Plasmón de Superficie , Técnicas del Sistema de Dos Híbridos
13.
Int J Mol Sci ; 16(10): 23572-86, 2015 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-26437401

RESUMEN

Aspartic acid semialdehyde dehydrogenase (ASADH) lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. Mutations in the asadh gene encoding ASADH produce an inactive enzyme, which is lethal. Therefore, in this study, we investigated the hypothesis that ASADH represents a new anti-Mycobacterium tuberculosis (MTB) target. An asadh promoter-replacement mutant MTB, designated MTB::asadh, in which asadh gene expression is regulated by pristinamycin, was constructed to investigate the physiological functions of ASADH in the host bacteria. Bacterial growth was evaluated by monitoring OD600 and ASADH expression was analyzed by Western blotting. The results showed that the growth and survival of MTB::asadh was completely inhibited in the absence of the inducer pristinamycin. Furthermore, the growth of the mutant was rigorously dependent on the presence of the inducer in the medium. The starved mutant exhibited a marked reduction (approximately 80%) in the cell wall materials compared to the wild-type, in addition to obvious morphological differences that were apparent in scanning electron microscopy studies; however, with the addition of pristinamycin, the cell wall contents and morphology similar to those of the wild-type strain were recovered. The starved mutant also exhibited almost no pathogenicity in an in vitro model of infection using mouse macrophage J774A.1 cells. The mutant showed a concentration-dependent recovery of pathogenicity with the addition of the inducer. These findings implicate ASADH as a promising target for the development of novel anti-MTB drugs.


Asunto(s)
Antituberculosos/farmacología , Aspartato-Semialdehído Deshidrogenasa/metabolismo , Mycobacterium tuberculosis/enzimología , Animales , Western Blotting , Línea Celular , Pared Celular/efectos de los fármacos , Pared Celular/metabolismo , Electroforesis en Gel de Agar , Ratones , Mutación/genética , Mycobacterium tuberculosis/citología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , Regiones Promotoras Genéticas/genética , Reproducibilidad de los Resultados
14.
Yao Xue Xue Bao ; 49(2): 230-6, 2014 Feb.
Artículo en Zh | MEDLINE | ID: mdl-24761614

RESUMEN

The crude extracts of the fermentation broth from a marine sediment-derived actinomycete strain, Saccharothrix sp. 10-10, showed significant antibacterial activities against drug-resistant pathogens. A genome-mining PCR-based experiment targeting the genes encoding key enzymes involved in the biosynthesis of secondary metabolites indicated that the strain 10-10 showed the potential to produce tetracenomycin-like compounds. Further chemical investigation of the cultures of this strain led to the identification of two antibiotics, including a tetracenomycin (Tcm) analogs, Tcm X (1), and a tomaymycin derivative, oxotomaymycin (2). Their structures were identified by spectroscopic data analysis, including UV, 1D-NMR, 2D-NMR and MS spectra. Tcm X (1) showed moderate antibacterial activities against a number of drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) pathogens, with the MIC values in the range of 32-64 microg x mL(-1). In addition, 1 also displayed significant cytotoxic activities against human cancer cell lines, including HL60 (leukemia), HepG2 (liver), and MCF-7 (breast) with the IC 50 values of 5.1, 9.7 and 18.0 micromol x L(-1), respectively. Guided by the PCR-based gene sequence analysis, Tcm X (1) and oxotomaymycin (2) were identified from the genus of Saccharothrix and their 13C NMR data were correctly assigned on the basis of 2D NMR spectroscopic data analysis for the first time.


Asunto(s)
Actinomycetales/química , Antibacterianos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Actinomycetales/genética , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Benzodiazepinonas/química , Benzodiazepinonas/aislamiento & purificación , Benzodiazepinonas/farmacología , Línea Celular Tumoral , Minería de Datos/métodos , Farmacorresistencia Bacteriana , Enterococcus faecalis/efectos de los fármacos , Fermentación , Genómica , Humanos , Concentración 50 Inhibidora , Biología Marina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Naftacenos/química , Naftacenos/aislamiento & purificación , Naftacenos/farmacología , Filogenia , Staphylococcus epidermidis/efectos de los fármacos
15.
J Nat Prod ; 76(9): 1535-40, 2013 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-23972215

RESUMEN

Three new polyketide compounds (1-3), a new quinolone alkaloid (4), and seven known polyketide derivatives were identified from the cultures of Penicillium sp. I09F 484, a strain isolated from the rhizosphere soil of the plant Picea asperata from Kanas Lake, Xinjiang, China. Their structures were elucidated by extensive spectroscopic data analysis. The absolute configurations of 1 and 4 were established by quantum chemical time-dependent density functional theory electronic circular dichroism calculation and Marfey's method, respectively. Compounds 1 and 2 displayed inhibitory activity against New Delhi metallo-ß-lactamase 1 with IC50 values of 94.9 and 87.9 µM, respectively.


Asunto(s)
Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Penicillium/química , Policétidos/aislamiento & purificación , Policétidos/farmacología , Quinolonas/aislamiento & purificación , Inhibidores de beta-Lactamasas , Alcaloides/química , China , Dicroismo Circular , Cristalografía por Rayos X , Concentración 50 Inhibidora , Estructura Molecular , Policétidos/química , Quinolonas/química , Quinolonas/farmacología , Rizosfera , beta-Lactamasas
16.
J Nat Prod ; 76(11): 2153-7, 2013 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-24164206

RESUMEN

A PCR-based genetic screening experiment targeting the dTDP-glucose-4,6-dehydratase gene revealed that a marine sediment-derived strain, Streptomyces sp. 7-145, had the potential to produce glycosidic antibiotics. Chemical investigation of culture extracts of this strain yielded two new 6-deoxyhexose-containing antibiotics, 11',12'-dehydroelaiophylin (1) and 11,11'-O-dimethyl-14'-deethyl-14'-methylelaiophylin (2), together with four known elaiophylin analogues (3-6). Their structures were determined by extensive NMR, MS, and CD analyses. Compounds 1, 3, 4, and 6 showed good antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci pathogens.


Asunto(s)
Antibacterianos/aislamiento & purificación , Macrólidos/aislamiento & purificación , Streptomyces/química , Antibacterianos/química , Antibacterianos/farmacología , Macrólidos/química , Macrólidos/farmacología , Biología Marina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Reacción en Cadena de la Polimerasa , Vancomicina/farmacología
17.
Kidney Blood Press Res ; 37(1): 15-23, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23445897

RESUMEN

BACKGROUND: Matrix Gla protein (MGP) is a molecular determinant regulating vascular calcification of the extracellular matrix. However, it is still unclear how MGP may be involved in crystal formation in the kidney of hyperoxaluric rats. METHODS: Male Sprague-Dawley rats were divided into the hyperoxaluric group and control group. Hyperoxaluric rats were administrated by 0.75% ethylene glycol (EG) for up to 8 weeks. Renal MGP expression was detected by the standard avidin-biotin complex (ABC) method. Renal crystal deposition was observed by a polarizing microscope. Total RNA and protein from the rat kidney tissue were extracted. The levels of MGP mRNA and protein expression were analyzed by the real-time polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Hyperoxaluria was induced successfully in rats. The MGP was polarly distributed, on the apical membrane of renal tubular epithelial cells, and was found in the ascending thick limbs of Henle's loop (cTAL) and the distal convoluted tubule (DCT) in hyperoxaluric rats, its expression however, was present in the medullary collecting duct (MCD) in stone-forming rats. Crystals with multilaminated structure formed in the injurious renal tubules with lack of MGP expression.MGP mRNA expression was significantly upregulated by the crystals' stimulations. CONCLUSION: Our results suggested that the MGP was involved in crystals formation by the continuous expression, distributing it polarly in the renal tubular cells and binding directly to the crystals.


Asunto(s)
Proteínas de Unión al Calcio/biosíntesis , Proteínas de la Matriz Extracelular/biosíntesis , Hiperoxaluria/metabolismo , Cálculos Renales/metabolismo , Túbulos Renales/metabolismo , Animales , Glicol de Etileno/toxicidad , Hiperoxaluria/inducido químicamente , Hiperoxaluria/patología , Cálculos Renales/inducido químicamente , Cálculos Renales/patología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Masculino , Ratas , Ratas Sprague-Dawley , Proteína Gla de la Matriz
18.
Front Microbiol ; 14: 1168052, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37138606

RESUMEN

Introduction: With the increasingly serious problem of bacterial drug resistance caused by NDM-1, it is an important strategy to find effective inhibitors to assist ß-lactam antibiotic treatment against NDM-1 resistant bacteria. In this study, PHT427 (4-dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide) was identified as a novel NDM-1 inhibitor and restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1. Methods: We used a high throughput screening model to find NDM-1 inhibitor in the library of small molecular compounds. The interaction between the hit compound PHT427 and NDM-1 was analyzed by fluorescence quenching, surface plasmon resonance (SPR) assay, and molecular docking analysis. The efficacy of the compound in combination with meropenem was evaluated by determining the FICIs of Escherichia coli BL21(DE3)/pET30a(+)-bla NDM-1 and Klebsiella pneumoniae clinical strain C1928 (producing NDM-1). In addition, the mechanism of the inhibitory effect of PHT427 on NDM-1 was studied by site mutation, SPR, and zinc supplementation assays. Results: PHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 µmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-bla NDM-1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. The mutation of Asn220 and Gln123 abolished the affinity of NDM-1 by PHT427 via SPR assay. Discussion: This is the first report that PHT427 is a promising lead compound against carbapenem-resistant bacteria and it merits chemical optimization for drug development.

19.
Neuropsychiatr Dis Treat ; 19: 801-809, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37077708

RESUMEN

Purpose: To explore the correlation between aggressive behavior and impulsive and aggressive personality traits in inpatients with schizophrenia. Methods: In total, 367 inpatients with schizophrenia were divided into two groups: the aggressive group and the non-aggressive group. We assessed inpatients' psychotic symptoms as well as their aggressive and impulsive personality traits using the Positive and Negative Symptom Scale, the Barratt Impulsiveness Scale, and the Buss-Perry Aggression Questionnaire. Results: Compared with the scores of inpatients in the non-aggressive group, the total Buss-Perry Aggression Questionnaire, subscale, and Barratt Impulsiveness Scale behavioral factor scores in those in the aggressive group were higher (p < 0.05). The results of logistic regression analysis suggested that a high Positive and Negative Symptom Scale positive factor score (odds ratio = 1.07) and a high Buss-Perry Aggression Questionnaire physical aggression score (odds ratio = 1.02) were risk factors for aggressive behavior. Conclusion: Hospitalized patients with schizophrenia with more severe positive symptoms and aggressive traits may be more prone to aggressive behavior.

20.
Bioorg Med Chem Lett ; 22(19): 6151-4, 2012 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-22939698

RESUMEN

Two new streptothricins (1 and 2) and a new streptothricin acid derivative (3), all with the carbamoyl group substituted at C-12 of the gulosamine moiety, together with the known N(ß)-acetylstreptothricin D acid (4), have been isolated from the culture broth of Streptomyces sp. I08A 1776. The structures of the new compounds were determined by MS, CD, and 1D and 2D NMR spectroscopic data analysis. The isolated compounds were evaluated for antibacterial and antifungal activities. Streptothricin E (6) showed potent activity against the clinically isolated extensively drug-resistant Mycobacterium tuberculosis with MIC values of 0.25-0.5µg/mL.


Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Streptomyces/química , Estreptotricinas/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Estreptotricinas/química , Estreptotricinas/aislamiento & purificación
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